University of Minnesota Hospital and Clinics Minneapolis, MN presents Kurt Amplatz MD University of Minnesota Hospital and Clinics Minneapolis, MN presents Recorded at the 3rd Pediatric Interventional Cardiac Symposium, September 1999, in Chicago, Illinois.

Nickel toxicity: what is the issue?

Société Française de Cardiologie Conclusions: CardioSEAL 1. no nickel 2. less bulky 3. better endothelialization

CardioSEAL metal The metal of our competitor is MP35N with a 33% nickel content!

Amplatzer® devices from Felix Berger MD Fig. 1 Implanted high-profile Amplatzer devices

Nickel allergy Nine percent of the population is allergic to nickel. However implantation of nickel-containing prostheses and devices virtually never causes problems.

Allergy and nickel-containing implants Dear Dr. Amplatz, Many thanks for answering about percutaneous closure of ASD with the Amplatzer device in patients with allergy to nickel. As you know, I decided to perform the procedure in this young lady that presented with a cutaneous allergic reaction to nickel: The procedure was uneventful and at one month follow-up, no shunt was detected by Echo and she is doing fine… Eustaquio Onorato MD Clinica San Rocco Di Franciacorta SpA Ome, Italy

An essential element Nickel is an essential element for nutrition. Lack of nickel results in retarded body growth, anemia, and increased neonatal mortality in experimental animals. Inorganic elements essential for life: Cu, Zn, Se, Mg, Mn, Ca, Fe, Mo, Ni, etc

Toxicity Paracelsus (1493–1541): The factor determining whether a compound is toxic or not depends on the dose

Intake of nickel Daily intake of nickel in the United States ranges from 300 to 600 micrograms per day. Most of the ingested nickel is excreted via feces, urine, bile, and sweat.

Exposure to nickel Nickel-containing alloys used in: coins (quarters, nickels, euros) knives, forks, spoons, etc implants: wires, clips, coils, stents, nails, cava filters, prostheses, heart valves, pacemakers, etc

Anodic corrosion test Fig. 2 Nitinol wire corroded by anodic dissolution for 2 minutes at 6 mA. Pits and corrosion products are obvious.

Explanted orthodontal arch wires Control Explanted wire Fig. 3 Nitinol arch wire explanted at 1 month shows no evidence of corrosion.

Implanted Amplatzer devices Amin Z, et al. Circulation 1999;100:320-328 Fig. 4 Amplatzer devices implanted in a dog with 2 ventricular septal defects. The second device is a "dog-bone" design that was investigated in some animals.

Follow-up at 1 week Fig. 5 One week after implantation, there is complete closure of the communication.

Follow-up at 1, 14, and 18 months Fig. 6 At one-month follow-up, there is no change. Inspection at 14 and 18 months (not shown) confirms the same and demonstrates no aortic or tricuspid insufficiency.

Cardioscopy of right disks First device Second device Fig. 7 Right side of the device is completely endothelialized.

Cardioscopy of the left disks and valves Fig. 8 Left side of the device shows complete endothelialization, except of the post. Cardioscopy, in other views (not shown), confirms normal aortic, mitral, and tricuspid valves.

Explanted Amplatzer devices First device Second device Fig. 9 Amplatzer devices, explanted at 18 months and polyester fabric removed, are indistinguishable from brand-new devices. There is not a single wire broken.

Human experience September 1995: first implant in a patient Masura J, et al. Cathet Cardiovasc Diagn 1997;42:388-393 September 1995: first implant in a patient November 1998: device is intact and shows only total heart motion

Nickel toxicity Nickel toxicity occurs exclusively in nickel refineries due to inhalation of nickel carbonyl, Ni(CO)4, being part of the Mond process.

Explanted devices under light microscopy Fig. 10 The explanted Amplatzer devices under light microscopy reveal a perfectly shiny surface with no evidence of pitting.

Explanted devices under scanning electromicroscopy End disk Disk with female screw Fig. 11 Scanning electromicroscopy again reveals no corrosion of the explanted devices.

Explanted devices at x3000 magnification Control Explanted wire Fig. 12 At x3000 magnification, the explanted Amplatzer devices still show no corrosion. At this magnification, 1 mm would measure 3 m!

Nickel corrosion in a biologic environment A corrosion of 10% would produce a huge crater at 3000 times magnification and the daily dose of nickel would have been 15.4 micrograms, 33 times less than the daily intake.

Conclusion Edie JW, et al. Angle Orthod 1981;51,4:319-24 “In conclusion, the results reported here suggest that there is no reason to believe that Nitinol wires are any more subject to corrosion than stainless steel wires in an environment that is typical of clinical service.” Edie JW, et al (1981)