Rebuttal with regards to “Device‐associated thrombus formation after left atrial appendage occlusion: A systematic review of events reported with the Watchman, the Amplatzer Cardiac Plug and the Amulet”

We thank Koniari et al. for their interest and comments on our article. We agree that allergic reaction to nitinol is an important aspect to consider, as nitinol is widely used in interventional cardiology devices (coronary stents, atrial septal defect (ASD) or patent foramen ovale (PFO) occluders, left atrial appendage (LAA) occluders, TAVI) and could potentially lead to adverse clinical consequences. Nitinol is a nickeltitanium alloy and nickel is a potential sensitizer which can give rise to hypersensitivity-associated events. However, with conflicting reports in the setting of percutaneous coronary intervention [1–3], there is currently little evidence that nickel allergy has a cause-effect relationship with adverse cardiovascular clinical events. There are indeed reported cases of symptoms of allergic reaction to metal in case of PFO or ASD closure, mainly related to the occurrence of postimplantation chest discomfort or palpitations but without any evidence of an associated increase in the occurrence of device-associated thrombosis (DAT) [4–6]. Moreover, in a large registry including 418 patients implanted with an Amplatzer ASD or PFO device, the rate of DAT was 0% at 1 month TEE follow-up [7]. As reported in our article, DAT after LAA occlusion is most likely multifactorial with risk factors including patient, device and anatomic characteristics. The possibility that nickel allergy may result in DAT cannot be firmly excluded. However, this is most likely a rare etiology as reported in PFO/ASD devices [7–9]. Furthermore, in reported cases of DAT, the presence of postimplantation allergic reaction was not described. To the best of our knowledge, in the rare cases where an LAA occluder had to be explanted, there was no available histologic finding implicating an allergic reaction. The Amplatzer Cardiac Plug and the Amulet (St. Jude Medical/Abbott, St Paul, MN, USA) are composed of nitinol wire with an inner ultra-thin membrane of expanded polytetrafluoroethylene, which seems to be less thrombogenic than the metallic framework of other devices used in PFO occlusion [7,10]. The WATCHMAN device (Boston Scientific, Natick, MA, USA) consists of a nitinol frame also covered with permeable polyethylene terephthalate membrane. Therefore, we believe that nickel hypersensitivity testing may be considered in patients with an allergic history before device implantation, and nickel hypersensitivity may be relevant in DAT cases with no other identified risk factors. Further documentation of metal allergy and complimentary investigations in the setting of DAT should be considered in future studies on LAA occlusion.