Verma, Atul

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.

Background: Ablation of ventricular tachycardia (VT) is limited by the inability to create penetrating lesions to reach intramyocardial origins. Intramural needle ablation using in-catheter, heated saline-enhanced radio frequency (SERF) energy uses convective heating to increase heat transfer and produce deeper, controllable lesions at intramural targets. This first-in-human trial was designed to evaluate the safety and efficacy of SERF needle ablation in patients with refractory VT. Methods: Thirty-two subjects from 6 centers underwent needle electrode ablation. Each had recurrent drug-refractory monomorphic VT after implantable cardioverter defibrillator implantation and prior standard ablation. During the SERF study procedure, one or more VTs were induced and mapped. The SERF needle catheter was used to create intramural lesions at targeted VT site(s). Acute procedural success was defined as noninducibility of the clinical VT after the procedure. Patients underwent follow-up at 30 days, and 3 and 6 months, with implantable cardioverter defibrillator interrogation at follow-up to determine VT recurrence. Results: These refractory VT patients (91% male, 66±10 years, ejection fraction 35±11%; 56% ischemic, and 44% nonischemic) had a median of 45 device therapies (shock/antitachycardia pacing) for VT in the 3 to 6 months pre-SERF ablation. The study catheter was used to deliver an average of 10±5 lesions per case, with an average of 430±295 seconds of radiofrequency time, 122±65 minute of catheter use time, and a procedural duration of 4.3±1.3 hours. Acute procedural success was 97% for eliminating the clinical VT. At average follow-up of 5 months (n=32), device therapies were reduced by 89%. Complications included 2 periprocedural deaths: an embolic mesenteric infarct and cardiogenic shock, 2 mild strokes, and a pericardial effusion treated with pericardiocentesis (n=1). Conclusions: Intramural heated saline needle ablation showed complete acute and satisfactory mid-term control of difficult VTs failing 1 to 5 prior ablations and drug therapy. Further study is warranted to define safety and longer-term efficacy. Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT03628534 and NCT02994446.

Pulsed electrical field (PEF) energy is a promising technique for catheter ablation of cardiac arrhythmias. In this article, the key aspects that need to be considered for safe and effective PEF delivery are reviewed, and their impact on clinical feasibility is discussed. The most important benefit of PEF appears to be the ability to kill cells through mechanisms that do not alter stromal proteins, sparing sensitive structures to improve safety, without sacrificing cardiomyocyte ablation efficacy. Many parameters affect PEF treatment outcomes, including pulse intensity, waveform shape, and number of pulses, as well as electrode configuration and geometry. These physical and electrical characteristics must be titrated carefully to balance target tissue effects with collateral implications (muscle contraction, temperature rise, risk of electrical arcing events). It is important to note that any combination of parameters affecting PEF needs to be tested for clinical efficacy and safety. Applying PEF clinically requires knowledge of the fundamentals of this technology to exploit its opportunities and generate viable, durable health improvements for patients.

Background: Pulmonary vein (PV) stenosis is a highly morbid condition that can result after catheter ablation for PV isolation. We hypothesized that pulsed field ablation (PFA) would reduce PV stenosis risk and collateral injury compared with irrigated radiofrequency ablation (IRF). Methods: IRF and PFA deliveries were randomized in 8 dogs with 2 superior PVs ablated using one technology and 2 inferior PVs ablated using the other technology. IRF energy (25–30 W) or PFA was delivered (16 pulse trains) at each PV in a proximal and in a distal site. Contrast computed tomography scans were collected at 0, 2, 4, 8, and 12-week (termination) time points to monitor PV cross-sectional area at each PV ablation site. Results: Maximum average change in normalized cross-sectional area at 4-weeks was −46.1±45.1% post-IRF compared with −5.5±20.5% for PFA ( P ≤0.001). PFA-treated targets showed significantly fewer vessel restrictions compared with IRF ( P ≤0.023). Necropsy showed expansive PFA lesions without stenosis in the proximal PV sites, compared with more confined and often incomplete lesions after IRF. At the distal PV sites, only IRF ablations were grossly identified based on focal fibrosis. Mild chronic parenchymal hemorrhage was noted in 3 left superior PV lobes after IRF. Damage to vagus nerves as well as evidence of esophagus dilation occurred at sites associated with IRF. In contrast, no lung, vagal nerve, or esophageal injury was observed at PFA sites. Conclusions: PFA significantly reduced risk of PV stenosis compared with IRF postprocedure in a canine model. IRF also caused vagus nerve, esophageal, and lung injury while PFA did not.

Introduction: Recent trials using insertable cardiac monitors (ICMs) show high rates of atrial fibrillation (AF) in those at risk of developing AF based on demographics. Further identifying subsets who could benefit most from ICMs is desirable. We evaluated if the recently-developed HAVOC risk score which has predicted AF in cryptogenic stroke patients also predicts AF detection by ICMs in those without a recent stroke. Methods: Participants from the prospective REVEAL AF study, which reported frequent clinically unrecognized AF in patients at risk for AF (CHADS 2 scores ≥3 or =2 with ≥1 additional risk factor), with ICM data and not on anti-arrhythmic drugs were included. Ischemic stroke <1 year ago excluded participation. HAVOC scores were calculated using points for hypertension (2), age ≥75 (2), valvular disease (2), vascular disease (1), obesity (1), congestive heart failure (4), and coronary artery disease (2). Prior stroke, an AF outcome, generally not a cause, is not included. Score classification is: low (0-4), intermediate (5-9), or high (10-14). Corresponding AF detection rates were compared via the log-rank test. Results: Among 391 participants, 95 (24%), 241 (62%), and 55 (14%) had low, intermediate, and high HAVOC scores, respectively. At 18 months, AF incidence was significantly less for those with low (19.5%) vs intermediate (32.1%) or high (34.2%) scores (p=0.045, Figure). At 18 months, AF incidence was similar among those with (n=79) vs. without (n=312) a history of remote stroke (27.1% vs. 29.9%; p>0.05, median time from stroke to ICM insertion=4 years). Conclusions: The HAVOC risk score identified a subset of high risk individuals at greatest risk of developing AF. AF incidence rates were similar among those with and without prior remote stroke. Remote strokes may not be a strong predictor of AF in this population. HAVOC scores could be a useful approach to identify those at high likelihood of manifesting AF, as best documented by long-term monitoring.