First-in-human clinical series of a novel conformable large-lattice pulsed field ablation catheter for pulmonary vein isolation

Abstract

Aims: Pulsed field ablation (PFA) has significant advantages over conventional thermal ablation of atrial fibrillation (AF). This first-in-human, single-arm trial to treat paroxysmal AF (PAF) assessed the efficiency, safety, pulmonary vein isolation (PVI) durability and one-year clinical effectiveness of an 8 Fr, large-lattice, conformable single-shot PFA catheter together with a dedicated electroanatomical mapping system.

Methods and results: After rendering the PV anatomy, the PFA catheter delivered monopolar, biphasic pulse trains (5-6 s per application; ∼4 applications per PV). Three waveforms were tested: PULSE1, PULSE2, and PULSE3. Follow-up included ECGs, Holters at 6 and 12 months, and symptomatic and scheduled transtelephonic monitoring. The primary and secondary efficacy endpoints were acute PVI and post-blanking atrial arrhythmia recurrence, respectively. Invasive remapping was conducted ∼75 days post-ablation. At three centres, PVI was performed by five operators in 85 patients using PULSE1 (n = 30), PULSE2 (n = 20), and PULSE3 (n = 35). Acute PVI was achieved in 100% of PVs using 3.9 ± 1.4 PFA applications per PV. Overall procedure, transpired ablation, PFA catheter dwell and fluoroscopy times were 56.5 ± 21.6, 10.0 ± 6.0, 19.1 ± 9.3, and 5.7 ± 3.9 min, respectively. No pre-defined primary safety events occurred. Upon remapping, PVI durability was 90% and 99% on a per-vein basis for the total and PULSE3 cohort, respectively. The Kaplan-Meier estimate of one-year freedom from atrial arrhythmias was 81.8% (95% CI 70.2-89.2%) for the total, and 100% (95% CI 80.6-100%) for the PULSE3 cohort.

Conclusion: Pulmonary vein isolation (PVI) utilizing a conformable single-shot PFA catheter to treat PAF was efficient, safe, and effective, with durable lesions demonstrated upon remapping.

Keywords: Atrial fibrillation; Catheter ablation; Electroanatomical mapping system; Lesion durability; Pulsed field ablation; Single-shot.

Graphical Abstract

Figure 1

Single-shot pulsed field ablation catheter and pulsed field ablation system. The system includes the (A and B) single-shot PFA catheter and (C) the integrated mapping system, PF and RF generators, and irrigation pump. (A) The catheter has an electrode array composed of a compressible nitinol-based lattice that contains six pairs of mini-electrodes. PF energy emanates from the entire lattice framework as the six sections of the lattice are independently and sequentially energized. (B) The lattice is expandable up to 34 mm. PF, pulse field; RF, radiofrequency.

Figure 2

Rendering of left atrial and pulmonary vein anatomies with the PFA catheter. (A) The large-lattice catheter is shown along with a J-tip guidewire in various shapes—from a disk/pancake (top), deployed/basket (middle) to elongated (bottom) configurations. (B) To render the left atrial and pulmonary vein anatomies, the catheter is simply manoeuvred within the chamber and elongated into each pulmonary vein (see online Supplementary material online, Video S1 for a video example of this).

Figure 3

Pulmonary vein isolation using the PFA catheter. (A) A screenshot of the electroanatomical mapping system is shown with shadows (green shadows) of where the PFA lesions were placed, and the location of the ablation catheter in the right inferior pulmonary vein (white arrows) in both posterior (left) and superior (right) views. The PFA catheter (white arrows) is also shown at the left superior pulmonary vein antrum in a large basket configuration on fluoroscopy (B) and on intracardiac echocardiography (C). While not formally analysed, PVs were typically acutely isolated with the first PF application; subsequent successively proximal applications extended the level of isolation and acted as bonus lesions to enhance durability. See online Supplementary material online, Video S2 for an example of PFA of a PV.

Figure 4

Patient flow diagram. The overall patient population and individual PULSE1 (n = 30), PULSE2 (n = 20), and PULSE3 (n = 35) cohorts are shown, along with the number of patients in each treatment cohort that underwent invasive remapping and reached 12-month follow-up.

Figure 5

Electroanatomical maps of different phases of pulsed field ablation treatment. Shown are bipolar voltage amplitude maps from three different patients (A) before and (C) after PFA treatment and from (D) Day 75 remap procedure. In (B), shadows of the PFA catheter are captured to denote the locations of each of the four PFA applications at each PV. The colour range is 0.1 (red)–1.0 mV (purple).

Figure 6

Durability of pulmonary vein isolation on invasive remapping. PVI durability for patients presenting for remapping from the total cohort (n = 60; bright blue bars) or the PULSE3 cohort (n = 26; dark blue bars), with 238 and 100 remapped veins, respectively. PVI durability is shown on a per-vein (left) or per-patient basis (right). The P-value comparing PULSE1/PULSE2 (n = 34) vs. PULSE3 (n = 26) is <0.01 for both per-vein and per-patient durability. PV, pulmonary vein; PVI, pulmonary vein isolation.

Figure 7

Freedom from atrial arrhythmia recurrence at 365 days. Shown are the Kaplan–Meier estimates of freedom from ≥30 s recurrence of AF/AFL/AT at 365 days in the total cohort (red line) and PULSE3 cohort (gold line). Note that due to no events observed in the PULSE3 cohort, the 95% confidence interval is calculated with Wilson’s method for binomial proportions. Comparing PULSE1/PULSE2 (n = 50) vs. PULSE3 (n = 16), P = 0.04 (log-rank test). The dotted line denotes the end of the 90-day blanking period. AF, atrial fibrillation; AFL, atrial flutter; AT, atrial tachycardia.