COOPERATIVE-PFA: A Three-Arm Randomized Controlled Trial

Abstract

BACKGROUND: Deep analgosedation (DAS) or general anesthesia is mandatory for pulsed-field ablation of atrial fibrillation. In contrast to DAS, general anesthesia (conventional or total intravenous anesthesia [TIVA]) requires airway management. To find the optimal sedation regimen, this study compared ketamine-remimazolam DAS and propofol-opioid TIVA with propofol-opioid DAS, focusing on sedation-related adverse events. METHODS: Patients indicated for atrial fibrillation catheter ablation were randomly assigned at a 1:1:1 ratio to: (1) DAS using intermittent propofol-opioid boluses (arm P), (2) continuous remimazolam-ketamine DAS (arm R), or (3) continuous propofol-opioid TIVA with secured airway (arm TIVA). Catheter ablation was performed using the FARAPULSE system (Boston Scientific, MA). The major exclusion criterion was obstructive sleep apnea syndrome. The primary end point was defined as a composite of hypoxemia, hypotensive, or hypertensive events requiring intervention or leading to procedure discontinuation. Secondary end points included hemodynamic instability events, procedure time, serious adverse events, and patient satisfaction. RESULTS: One-hundred twenty-seven patients (mean age 62.9±10.3 years, 35.1% women, 47.2% with paroxysmal atrial fibrillation) were enrolled and randomized to the P (n=42), R (n=43), or TIVA (n=42) arms. The primary end point occurred in 85.7% of P patients, 27.9% of R patients, and 66.7% of TIVA patients ( P <0.001), driven by hypoxemia in the P arm (100% of patients with the primary end point) and by hypotension in the TIVA arm (100%). The R arm showed a similar distribution of hypoxemia (50%) and hypotensive (66.7%) events. No differences were observed in mean procedural time, rate of serious adverse events, and assessment of patient satisfaction. CONCLUSIONS: In pulsed-field ablation procedures for atrial fibrillation, remimazolam-ketamine DAS was superior to propofol-opioid regimens (either boluses or continuous) and had the lowest risk of hypoxemia and hypotensive events. More than 80% of patients undergoing conventional propofol-opioid analgosedation experienced hypoxemia. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06013345.