Time-to-Effect-Based Dosing Strategy for Cryoballoon Ablation in Patients With Paroxysmal Atrial Fibrillation Results of the plusONE Multicenter Randomized Controlled Noninferiority Trial

Background: The optimal dosage of cryotherapy during cryoballoon ablation of pulmonary veins is still unclear. This trial tested the noninferiority of a novel, individualized, cryotherapy-dosing strategy for each vein. Methods and Results: This prospective, randomized, multicenter, noninferiority study included 140 patients with paroxysmal atrial fibrillation, which was refractory to antiarrhythmic drugs. Patients were randomly assigned to a conventional strategy of 180-second cryoballoon applications per vein with a bonus freeze (control group, n=70) or to a shorter-time application protocol, with 1 application that lasted the time required for electric block time to effect plus 60- and a 120-second freeze bonus (study group, n=70). Patients were followed with a long-term monitoring system of 30 days. At 1-year follow-up, no difference was observed in terms of free atrial fibrillation-recurrence rates: 79.4% in control versus 78.3% in study group (Delta=1.15%; 90% confidence interval, -10.33% to 12.63%; P=0.869). Time to effect was detected in 72.1% of veins. The control and study groups had similar mean number of applications per patient (9.62 versus 9.92.4; P=0.76). Compared with controls, the study group had a significantly shorter cryotherapy time (28.3 +/- 7 versus 19.4 +/- 4.3 minutes; P<0.001), left atrium time (104 +/- 25 versus 92 +/- 23 minutes; P<0.01), and total procedure time (135 +/- 35 versus 119 +/- 31 minutes; P<0.01). No differences were observed in complications or acute reconnections. Conclusions: The new time-to-effect-based cryotherapy dosage protocol led to shorter cryotherapy and procedure times, with equal safety, and similar acute and 1-year follow-up results, compared with the conventional approach.