Comparison of Amplatzer and Gore Cardioform occluder for patent foramen ovale closure in patients with nickel hypersensitivity

Abstract Background Although the lifetime stroke risk attributable to PFO is low, transcatheter PFO closure has demonstrated efficacy in secondary stroke prevention. Randomized trials have shown significant reductions in recurrent stroke risk compared to antithrombotic treatment alone. There are only two Food and Drug Administration and CE-approved devices for PFO closure: the Amplatzer PFO Occluder and the GoreCardioform Septal Occluder (GSO). Both devices are constructed from nitinol, an alloy of nickel and titanium. Nickel is a potent allergen responsible for type IV hypersensitivity in 20% of the population. While skin hypersensitivity, primarily expressed as contact dermatitis, is well-characterized, the impact of systemic exposure to nickel from implanted nitinol devices remains poorly understood. Purpose The aim of our analysis is to assess the potential influence of device selection in patients with known nickel hypersensitivity. Methods This is a post-hoc analysis of INSPIRE trial. Briefly, the INSPIRE (Investigation of Nickel Sensitization After Percutaneous Implantation of Patent Foramen Ovale Occluder) trial was an investigator-initiated, multicenter, prospective, double-blinded, randomized trial with blinded endpoint assessment, exploring whether patients with nickel hypersensitivity have an increased risk of adverse events following PFO closure. Nickel hypersensitivity was assessed using skin patch testing. The primary endpoint was device syndrome, a composite of patient-reported symptoms (chest pain, palpitations, migraines, dyspnea, and rash). In addition to the composite outcomes listed as the primary endpoint, the secondary endpoints included documented atrial arrhythmias atrial fibrillation (AF), atrial flutter, or supraventricular tachycardia, major or minor bleeding, ischemic or hemorrhagic stroke, and all-cause mortality. Results Between January 2021 and September 2024, a total of 96 patients were included in the analysis and randomized to receive either the Amplatzer PFO Occluder (N = 48) or the GSO (N = 48). A total of 28 patients (29.2%) had been diagnosed with nickel hypersensitivity: 4 (4.2%) had a weak positive reaction, 16 (16.7%) had a strong positive reaction, and 8 (8.3%) had an extremely positive reaction. Sixteen patients were randomized to the Amplatzer PFO Occluder, and 12 patients were randomized to the GSO. No significant difference was observed in baseline characteristics. The incidence of the primary endpoint was comparable between the Amplatzer group (N = 11, 68.8%) and the GSO group (N = 9, 75.0%) (p = 1.000). No significant differences were observed in any secondary endpoints. Conclusions Our prospective, double-blinded, randomized trial with blinded endpoint assessment demonstrated that no significant differences were observed between the Amplatzer PFO Occluder and the GSO. Further larger studies are needed to provide more definitive insights into this issue.