Pulsed ElectRic FiEld Versus Cryoballoon for PAF

AF is the most common sustained arrhythmia, substantially increasing morbidity and mortality, in addition of being a significant burden on healthcare systems worldwide. During the last decades, catheter ablation with radiofrequency (RF) energy has emerged as an alternative non-pharmacological therapy for AF patients who are intolerant to AADs.2 Catheter ablation is currently the most effective rhythm control strategy;3 its rationale lies in the elimination of atrial sites involved in AF initiation/maintenance. Specifically, studies have demonstrated a critical role of pulmonary veins (PVs) as a source of ectopic beats triggering AF paroxysms and that isolation of PVs (PVI) from the left atrium effectively prevents atrial tachyarrhythmia relapse in paroxysmal AF patients. In addition to point-by-point isolation, PVI can also be achieved with single-shot technologies (e.g., cryoballoon, RF balloon, laser balloon), which have been developed aiming at simplifying the procedure and minimizing the influence of operator's experience on procedural safety and success.

Cryoballoon ablation is currently the most widespread single-shot technique for PVI. Its safety and efficacy has been demonstrated to be superior to antiarrhythmic drug treatment4,5 and non-inferior to RF-based point-by-point PVI in randomized and non-randomized trials.

Both RF and cryothermy rely on thermal processes (heating or freezing, respectively) for cardiac tissue death induction. Despite significant technological improvements and a better understanding of the biophysics of thermal ablation, the main shortcoming of these techniques is the lack of tissue selectivity. Achieving contiguous, transmural cardiac lesions may be associated to an increased risk of collateral damage to surrounding tissues (e.g., phrenic nerve, esophagus, blood vessels).

PFA has emerged as a novel ablation technology, which involves the application of ultrarapid (microseconds to nanoseconds), high-amplitude electrical pulses. These pulses generate strong electric fields with an increase in cell membrane permeability and impaired cell homeostasis, which may promote cell death. In this perspective, PFA differs from the above-mentioned thermal energy sources since it does not rely on thermal processes to achieve ablation. Moreover, the treatment protocol can be designed to overcome/limit the risk of collateral tissue damage and improve cardiac lesion durability.

To date, the only PFA device with regulatory approval (CE-mark) is the multielectrode Farawave catheter (FarapulseTM-Boston Scientific Inc., Marlborough, Massachusetts, USA). The safety and efficacy of the system has been tested in two phase 3 studies enrolling paroxysmal and persistent AF patients, which demonstrated remarkable safety and lesion durability results. Similar observations were confirmed in multiple subsequent post-approval registries.

In addition, the safety and efficacy of the pentaspline FarapulseTM PFA catheter has been reported in several registries12,14, as well as a recent randomized study10 comparing this new technology versus traditional energy sources (e.g. radiofrequency and cryothermy). Our group has been actively involved since the earliest stages of the release of the Farapulse technology. We are one of the two sites worldwide to have all three approved PFA technologies. Our center experience with the FarapulseTM technology includes >600 atrial fibrillation procedures. All operators involved in the trial have performed at least 50 PFA cases and are considered opinion leaders in the field and with the technology.

Nonetheless, no data currently exist directly comparing the safety and long-term efficacy of single-shot PFA versus cryoballoon ablation. This study is designed to compare the well-established approach of cryoballoon ablation with the novel PFA-based single-shot Farapulse device for PVI of PAF in a randomized fashion.

Inclusion criteria

• Diagnosis of recurrent symptomatic non-valvular paroxysmal AF (PAF);
• Age 18 through 75 years-old on the day of enrollment;
• Willing and capable of providing written informed consent;
• Willing and capable of complying with all pre-, post- and follow-up testing andrequirements.

Exclusion criteria

• AF secondary to electrolyte imbalance, thyroid disease, valvular disease, or reversible or non-cardiac cause;
• Previous left atrium (LA) ablation or surgery;
• Previously diagnosed with persistent AF (greater than [>] 7 days in duration);
• Severe dilatation of the LA (LAD >50 millimeter (mm) antero-posterior diameter in case of transthoracic echocardiography (TTE));
• Pregnant or lactating (current or anticipated) at the time of catheter ablation;
• Current enrollment in any other study protocol where testing or results from that study may interfere with the procedure or outcome measurements for this study;
• Any other conditions such as, mental illness, addictive disease, terminal illness with a life expectancy of less than two years, extensive travel away from the research center that may lead to non-compliance with the protocol procedure or follow up.