Ann Thorac Surg 2001;72:762-763
© 2001 The Society of Thoracic Surgeons
Invited commentary
James D. Fonger, MDa
a Lenox Hill Hospital, New York, NY, USA
e-mail: jfonger{at}heartnet.org
The Silzone experience with mechanical heart valves suggests important lessons for new medical device development. Silver had been previously shown in vitro to be an effective broad-spectrum antimicrobial agent. In vitro toxicology and biocompatibility tests were satisfactory. In vivo chronic animal testing was performed with a subcutaneous pocket model to demonstrate reduced inflammation and infection of implanted inoculated patches treated with silver compared to controls. Safety and efficacy concerns appeared to have been addressed. When ion beam-assisted vapor deposition of silver on polyster fibrils was shown to result in a uniform and durable coating of the valve sewing ring, the way appeared to be cleared for the introduction of a relatively insignificant change to an excellent existing mechanical heart valve. The strength of healing to the adjacent native valve sewing ring, sterile or previously infected, in the face of silver coating had not been rigorously evaluated.
The Silzone-coated valve sewing ring received clearance for clinical use around the time that the multicenter randomized Artificial Valve Endocarditis Reduction Trial (AVERT) was launched, proposing to evaluate clinical performance in 4,400 patients over 3 years. After 18 months randomizing 807 patients to 398 Silzone implants, the study was stopped by the data monitoring committee and the valve removed from the market because of an unusually high rate of clinically significant paravalvular leaks. All Silzone coated valve products were voluntarily recalled by the manufacturer on January 7, 2000. The AVERT trial had served as a postmarket approval surveillance vehicle which identified the problem after an estimated 3,600 patients worldwide had already been implanted with the Silzone heart valve. A paper from Toronto at the June 2001 meeting of The Society for Heart Valve Disease confirms this finding in a random population of 176 implants. The authors concluded that Silzone coating was an independent predictor for endocarditis paravalvular leaks, and cardiac reoperation.
What went wrong? It appears that in an effort to enhance the antimicrobial properties of mechanical heart valves, the healing characteristics within the native valve annulus were impaired. The in vivo animal model did not adequately test for healing strength, and the regulatory process allowed Silzone to be approved for many patients while definitive clinical testing proceeded in a select few enrolled in the AVERT study. The unfortunate result was that some patients were placed at risk for additional heart surgery within 6 months of their initial operation. However, the incidence of late paravalvular leaks appears not to be increased, and routine annual surveillance without prophylactic valve explantation is therefore recommended. Unlike with prior structural failures of other mechanical valves, fortunately this problem is likely limited to the early postoperative period during which the valve is healing into the annulus.
This experience has important implications for those who feel that an antibiotic impregnated valve sewing ring may be the answer for use in the infected valve annulus. Although chronic animal valve testing is laborious and expensive, it may be the only way to uncover unexpected harmful findings related to an intended valve improvement. The competitive valve marketplace will inevitably be impatient, but also needs to be appropri-ately prudent with these life-sustaining devices. Once approved, a case could be made for the first large group of new patient implants to be done entirely within the confines of a study such as AVERT instead of allowing concurrent unrestricted use while the clinical data collected. It may be time to refocus the evaluation and approval of new devices away from exhaustive in vitro biocompatibility and toxicology testing where the results are often previously well established and redirect our efforts to better postmarket surveillance, particularly in the early phase of a new life-sustaining medical device release.
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The St. Jude "Silzone" valve: midterm results in treatment of active endocarditis
- Ralf G. Seipelt, Jaime F. Vazquez-Jimenez, Ingrid M. Seipelt, Andreas Franke, Khaled Chalabi, Friedrich A. Schoendube, and Bruno J. Messmer
Ann. Thorac. Surg. 2001 72: 758-762.
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