Nickel sensitization or desensitization after patent foramen ovale closure

Abstract Background Although the lifetime stroke risk associated with PFO is low, transcatheter PFO closure has demonstrated satisfying efficacy in secondary stroke prevention. Randomized trials have shown significant reductions in recurrent stroke risk compared to antithrombotic treatment alone, without raising major safety issues. There are only two Food and Drug Administration (FDA) and CE-approved devices for PFO closure: the AmplatzerPFO 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 post-hoc analysis is to evaluate potential sensitization or desensitization in patients without or with pre-existing nickel allergy, respectively. 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. 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). Ninety days after PFO closure, a total of 35 patients underwent repeat nickel skin patch testing. Of these, 12 (34.3%) were diagnosed with nickel hypersensitivity. No patient developed sensitization or desensitization after PFO closure. However, two patients with a strong positive reaction before the procedure had an extremely positive reaction after PFO closure, two patients with an extremely positive reaction before the procedure had a strong positive reaction after PFO closure, and one patient with a weak positive reaction before the procedure had a strong positive reaction after the intervention. Conclusions Our post-hoc analysis showed that no patient developed sensitization or desensitization after PFO closure. Further larger studies are needed to provide more definitive insights for nickel hypersensitivity secondary to PFO closure.