Predictors of Success for Pulmonary Vein Isolation With Pulsed-field Ablation Using a Variable-loop Catheter With 3D Mapping Integration: Complete 12-month Outcomes From inspIRE

BACKGROUND: We previously presented the safety and early efficacy of the inspIRE study (Study for Treatment of Paroxysmal Atrial Fibrillation [PAF] by Pulsed-field Ablation [PFA] System With Irreversible Electroporation [IRE]). With the study’s conclusion, we report the outcomes of the full pivotal study cohort, with an additional analysis of predictors of success. METHODS: InspIRE was a prospective, multicenter, single-arm clinical trial of drug-refractory paroxysmal atrial fibrillation. Pulmonary vein isolation was performed with a variable-loop circular catheter integrated with a 3-dimensional mapping system. Follow-up with 24-hour Holter was at 3, 6, and 12 months, as well as remote rhythm monitoring: weekly from 3 to 5 months, monthly from 6 to 12 months, and for symptoms. The primary effectiveness end point (PEE) was acute pulmonary vein isolation plus freedom from any atrial arrhythmia at 12 months. Additional subanalyses report predictors of PEE success. RESULTS: The patient cohort included 186 patients: aged 59±10 years, female 30%, and CHA2DS2-VASc 1.3±1.2. The previously reported primary adverse event rate was 0%. One serious procedure-related adverse event, urinary retention, was reported. The PEE was achieved in 75.6% (95% CI, 69.5%–81.8%). The clinical success of freedom from symptomatic recurrence was 81.7% (95% CI, 76.1%–87.2%). Simulating a monitoring method used in standard real-world practice (without protocol-driven remote rhythm monitoring), this translates to a freedom from all and symptomatic recurrence of 85.8% (95% CI, 80.8%–90.9%) or 94.0% (95% CI, 90.6%–97.5%), respectively. Multivariate analyses revealed that left ventricular ejection fraction ≥60% (adjusted odds ratio, 0.30) and patients receiving ≥48 PFA applications (adjusted odds ratio, 0.28) were independent predictors of PEE success. Moreover, PEE success was 79.2% in patients who received ≥12 PFA applications per vein compared with 57.1% in patients receiving fewer PFA applications. CONCLUSIONS: The inspIRE study confirms the safety and effectiveness of pulmonary vein isolation using the novel 3-dimensional mapping integrated circular loop catheter. An optimal number of PFA applications (≥48 total or ≥12 per vein) resulted in an improved 1-year success rate of ≈80%. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04524364

Table S2.Participant inclusion and exclusion criteria.

Inclusion criteria:
To participate in the study, candidates were required to meet ALL criteria.
2. Selected for AF ablation procedure by PVI.
3. Failed at least one AAD (class I to IV) as evidenced by recurrent symptomatic AF, or intolerable or contraindicated to the AAD. 4. Age 18-75 years.
13. Unstable angina pectoris within the past 6 months.
14. Anticipated cardiac transplantation, cardiac surgery, or other major surgery within the next 12 months.
15. Significant pulmonary disease (e.g., restrictive pulmonary disease, constrictive or chronic obstructive pulmonary disease) or any other disease or malfunction of the lungs or respiratory system that produces severe chronic symptoms.
16. Known significant PV anomaly that in the opinion of the investigator would preclude enrollment in this study.17.Has known pulmonary vein stenosis.

6.
Able and willing to comply with all pre-, post-and followsecondary to electrolyte imbalance, thyroid disease, or reversible or non-cardiac cause.2.Previous LA ablation or surgery.3. Patients known to require ablation outside the PV region (e.g., Cavotricuspid Isthmus region, atrioventricular reentrant tachycardia, atrioventricular nodal reentry tachycardia, atrial tachycardia, ventricular tachycardia and Wolff-Parkinson-White). 4. Previously diagnosed with persistent AF (> 7 days in duration).5. Severe dilatation of the LA (Left Atrium) >50mm antero-posterior diameter in case of Transthoracic Echocardiography).6. Presence of LA thrombus.7. Severely compromised left ventricular ejection fraction (LVEF) (LVEF <40%).8. Uncontrolled heart failure or New York Heart Association Class III or IV. 9. History of blood clotting, bleeding abnormalities or contraindication to anticoagulation (heparin, warfarin, or dabigatran).10.History of a documented thromboembolic event (including TIA) within the past 6 months.11.Previous Percutaneous coronary intervention / myocardial infarction within the past 2 months.
18. Acute illness, active systemic infection, or sepsis.19.Presence of intracardiac thrombus, myxoma, tumor, interatrial baffle or patch or other abnormality that precludes catheter introduction or manipulation.20.Severe mitral regurgitation.21.Presence of implanted pacemaker or Implantable Cardioverter-Defibrillator or other implanted metal cardiac device that may interfere with the IRE energy field.22. Presence of a condition that precludes vascular access (such as inferior vena cava filter).23.Significant congenital anomaly or a medical problem that in the opinion of the investigator would preclude enrollment in this study.24.Categorized as vulnerable population and requires special treatment with respect to safeguards of well-being.25.Current enrollment in an investigational study evaluating another device or drug.26.Women who are pregnant (as evidenced by pregnancy test if premenopausal), lactating, or who are of childbearing age and plan on becoming pregnant during the course of the clinical investigation.27.Life expectancy less than 12 months.28.Presenting contra-indications for the devices used in the study, as indicated in the respective IFU.Additional exclusion criteria for Wave I subjects: 29.Contraindication for MRI such as use of contrast agents due to advanced renal disease, claustrophobia etc. (at principal investigator discretion).30.Presence of iron-containing metal fragments in the body.31.Unresolved pre-existing neurological deficit.32.Uncontrolled significant Gastroesophageal Reflux Disease.

Figure S1 .
Figure S1.Effectiveness analysis in the per-protocol population, showing 12-month freedom

Figure S2 .
Figure S2.Forest plot of multivariable analysis of primary effectiveness endpoint using GEE

Table S3 .
Univariable and multivariable analysis of primary effectiveness endpoint (Wave II main study per protocol analysis set, N=186).