Pre-clinical evaluation of coronary stents and other endoprotheses

Transcription

1 B U D A P E S T U N I V E R S I T Y O F T E C H N O L O G Y A N D E C O N O M I C S F a c u l t y o f M e c h a n i c a l E n g i n e e r i n g S u m m a r y o f P h D d i s s e r t a t i o n W r i t t e n b y : G y ö r g y R i n g M. S c. i n M e c h a n i c a l E n g i n e e r i n g M. S c. i n B i o m e d i c a l E n g i n e e r i n g Pre-clinical evaluation of coronary stents and other endoprotheses S u p e r v i s e d b y : J á n o s D o b r á n s z k y B u d a p e s t

2 Prelude of the research In the civilised societies, diseases caused by arteriosclerosis (like cardiac-infarction) are affecting nations and is the most common cause of mortality [1]. One method of the treatment is expansion with a catheter, during which often a small wire mesh tube, a stent is implanted. The first blood vessel expanding implants were used in the late 1980s, and in the 1990s the implantation of stent significantly accelerated in the expansion of coronary arteries. In Hungary, the usage of coronary stents started in the early 1990s, and only one company is manufacturing and developing stents since The Tentaur stent that was developed and patented by László Major [2], between 1995 and 2006 had promoted healing for more than 2000 patients. To 2006 a K+F consortium developed the Sanocor stent, which is up to the mark to the recent worldwide manufactured stents, and its manufacturer received the CE-mark to this product in 2009 [3]. In Hungary, in comparison that at the beginning there were a couple of hundred implantations, the usage of the coronary stents significantly increased. In the past five years ( ) altogether there were more than a hundred thousand coronary stents implanted. At present in Hungary there is in twelve cities, altogether, sixteen cardiovascular centre-operating. The stent is a complicated engineering product of materials science and technological research. It contains technical characteristics, which can be understood with the combined knowledge from several specialities not just those within the classic technical or other natural science fields. For the doctors it has fundamental importance relating to the catheter therapy equipment, like the stents, that they should be able to insert them into such a professional system. This system allows the objective evaluation and the comparison based on quantitative parameters. The major part of the functional properties has remained on the level of subjective definition, or possibly in the categories that benefit the manufacturer s own interest. 1

3 Literature review In the literature review part of my dissertation I described the following: types, materials and manufacturing processes of the stents; other angioplasty equipment used during the stent implanting process. I reviewed the standards in relations to this topic, organised and summarized the main properties of the stents. The methods employed to determine the crush resistance and the radioscopic visibility criterion were described in detail as this is the foundation of my experimental work. During my main research period the MSZ EN standard has been used to provide prescriptive text on the topics: properties of stents under the topic of preclinical trials, specific requirements of artery stents. Nowadays, the MSZ EN ISO standard is in place. In this document are some characteristics on how the manufacturers have to classify the implants. However, only in a few cases does it define and provide the methodology of the examination. Upon completion of my examination of the literature on the topic: crush resistance of coronary stents, I concluded that I have to trial (as many as possible) the supporting methods documented in the different publications. In addition, I need to evaluate these methods using an analytical approach and identify the most optimal solution. Furthermore, I have to determine the parameters which describe the properties more accurately than previously before, together with suitability to compare the crush resistance of the stents. With regard to the literature on the visibility, it can be stated that I have not found any such a measuring method for the visibility of the stents that satisfies all the following criteria: objective classification of the parameter, provides a numeric result, suitability to compare different stents (i.e. size and type). Irodalmi hivatkozások listája [1] Karádi I.: Infarktus és koleszterin. karadi/ karadi.html ( ). [2] Major L: Endoluminális tágítóbetét. Magyar szabadalom, P ,

4 [3] Dobránszky J, Major L, Ginsztler J, Dévényi L: Koszorúértágítóbetétek anyagai és gyártástechnológiája. OGÉT-2009 XVII. Nemzetközi Gépész Találkozó, Mûszaki Szemle különszám (2009) Objectives With the knowledge facts associated with this subject and problems that evolved while defining my targets, I took into account the importance of answering the open questions and the demands of modern industry. Therefore my aims are as follows: 1. To develop a new examination method, which gives the crush resistance of the balloon expanded stents through compression load on multiple generatrix, and to test this method on stents with different geometric properties. 2. To determine the factors (especially the effect of the stent geometry), which influence the results received by the radial compressing test developed. 3. To develop an examination method, which evaluates objectively and makes comparable the radioscopic visibility of the stents and also results in a quantitative visibility parameter. Testing the method on stents with different properties. 4. To examine the correlations between the visibility parameter and the test characteristics of the procedure used for the visibility test. Summary For the topic of the crush resistance, I used two different examining procedures in accordance with the standard: compression between two parallel plates and compression along the circumference with support that provides equal load. In the first case, according to the literature and my own findings, I carried out several compression tests using two-, three- and four-generatrix, but I finally decided that the flattening test 3

5 between two parallel planes produced the most optimal results. Using this method, I examined coronary stents made from the material 316LVM, with exactly identical manufacturing parameters but with a diameter expanded to different sizes. For the evaluation I defined a radial load capacity classifying parameter (flattening force, flattening resistance, conventional flattening resistance and flattening stiffness) and concluded that at from the stents examined with the increase of the diameter, the value of these parameters did reduce proportionately. I proved that the most sensitive index number is the flattening stiffness used to grade the dependency on the diameter. The compression test along the circumference was carried out with a purposely designed unit. For the test, stents with the same type, material (316LVM) and size, but with different electro-polished parameters, and therefore different weight and strut width were used. The characteristic of the force-stent diameter graph taken from the standard, further to the displaying properties of the measuring system, was identical to the aspect of the graph resulting from the compression between two parallel plates. For the evaluation of the results I defined the crush resistance parameters (crushing force, crushing resistance, conventional crushing resistance and crushing stiffness) and concluded that the value of these parameters are increasing in proportion to the increase of the weight in the stents examined. The most sensitive index number from the parameters outlined earlier is the crushing stiffness used to grade the dependence of the weight. Using the two examination methods, the newly developed classifying parameters (i.e. based on the stents mechanical properties) can be used in practice in comparison tests for stents, which also can be used by doctors, in case of the evaluation of stent technical parameters. For the topic of the visibility I pioneered (i.e. until now method was non-existent) a new measurement method, which objectively classifies this parameter, providing a numerical result, as well as being suitable for the comparison of different stents (i.e. type and size). The method determines the relative visibility to the background on the X-ray microscope s images, created in the clinical practice with the beam voltage and cathode heating parameters. This relative visibility index (XRV REL ) describes the stent itself with a given screening condition, and it is also suitable to quantitatively evaluate the visibility of different stents (i.e. type, material, 4

6 and size) with the same screening conditions. An absolute visibility index was also defined, which ensures that the value of the percentage visibility is never greater than 100%. The stents with different weight, which were also used for the compression tests, were also examined before the nonexpanded diameter stage. From this test, I concluded that the relative visibility index lines, in function to the weight, can also be used as visibility master-graphs. With this, the visibility can be determined without the X-ray microscopic examination of the stent with the given material and size from the visibility master-graph (XRV REL = f(m)) based on the weight. Theses New scientific results Thesis 1 [1] During the course of my studies I introduced some new material testing index numbers based on the typical mechanical properties of the stents (i.e. mesh tube): flattening force, flattening resistance, conventional flattening resistance and flattening stiffness. These new index numbers are used to determine the radial load capacity of the stents associated with the crush test between two parallel planes. From the findings, I came to the conclusion, that with the increase of the expansion diameter of the Sanocor stent, the radial load capacity decreases. To demonstrate this, the most sensitive index number is the flattening stiffness. Thesis 2 [1] During the course of my studies I introduced some new materials testing index numbers based on the typical mechanical properties of the stents (i.e. mesh tube): crushing force, crushing resistance, conventional crushing resistance and crushing stiffness. These new index numbers are used to determine the crush resistance of the stents relating to the crush test with load along the circumference. From the findings, I came to the conclusion, that with the increase of the mass of the Sanocor stent, the crush resistance also increases. To demonstrate this, the most sensitive index number is the structural crushing stiffness. 5

7 Thesis 3 [2] [3] For this study I developed a new testing procedure to determine the radioscopic visibility of the stents. A relative visibility index was established, which provides a quantitative evaluation for the radioscopic visibility of the stents. In addition, it is also suitable to compare different stents (i.e. type, material, diameter or length) with the same screening parameter. Thesis 4 [2] [3] To determine the radioscopic visibility of the stents, I defined the absolute visibility index. This index evaluates (numerically) the radioscopic visibility of the stents on a scale of 0 and 100%, and is also suitable to compare different stents (i.e. type, material, diameter or length) with the same screening parameter. Thesis 5 [2] [3] To determine the radioscopic visibility of the stents, I developed a new procedure, which allows the relative visibility index of the stents of the same material to be determined of the relative visibility index of the stents of the same material, together with the size (i.e. length and diameter) without individual radioscopic examination. To achieve this, it is sufficient to develop the visibility master-graph (the relative visibility index mass function) for any optional stent made from the same material and of the same size. Utilization of the results In my dissertation, I provided a summary of the main geometrical and functional characteristics of the coronary stents, in which the technical content of these properties are defined. Until now, in case of the coronary stents, the major parts of the functional properties have remained on the level of subjective definition, or possibly in the categories that benefit the manufacturer s own interest. In addition, I have also provided the Hungarian and English descriptions of the various properties, designed to support improved communications between the Hungarian specialists working in this field. In case of the crush resistance the physicians are not in an easy position as they often come across measurements that are not compara- 6

8 ble, difficult to define and results in different dimensions. During my experimental study I developed a classification system that clearly separates the procedural types for the crush resistance examination. In the standard these procedural types are separated, unlike in the industry today, where these procedures are often mixed. For these procedural types I defined the classification parameters in accordance with the standard. In essence, using these parameters, it is possible to compare the products from different manufacturers. In the case of the visibility the physicians find themselves in an even worse situation as than that mentioned earlier. A doctor is able to monitor the position of the stent during the implanting procedure using an X-ray machine. However, where the visibility of the stent is also very important, there did not exist, any product parameter which classifies the visibility characteristics in an objective and quantitative manner. In the other part of my research I defined a measurement procedure, which now provides a quantitative evaluation of the stent s visibility. Furthermore, this method now permits an objective comparison. In summarising my research, the request from the medical users (i.e. the stents are fitted into a professional system, which allows the objective rating as well as the comparison with quantitative parameters) regarding the crush resistance and the visibility, has been fulfilled by the classification procedures and by the defined, quantitative, objective parameters stated in my dissertation. This achievement has obvious and practical advantages in the daily working lives of the doctors and engineers. Publication of the results 7 [1] Ring Gy, Bognár E, Dobránszky J: Testing Method of Stent s Radial Force. Gépészet 2008, G-2008-N-4 n4.pdf 5 oldal (ISBN ) [2] Ring Gy, Bognár E, Bálint-Pataki Zs, Dobránszky J: Different properties of coronary stents. Anyagok Világa Materials World, 7 (2007:2) [3] Ring Gy, Bognár E, Dobránszky J: Koszorúérsztentek vizsgálati lehetõségei. XXIV. Neumann Kollokvium december Veszprém, nk2005.pdf ; március 2

9 Other publications [4] Bognár E, Ring Gy, Dobránszky J: Koszorúérsztentek anyagvizsgálata. Anyagvizsgálók Lapja. 14 (2004:4) [5] Bognár E, Ring Gy, Albrecht K, Dobránszky J, Ginsztler J: Haemocompatible Coatings of Coronary Stents. Advances in Science and Technology. 49 (2006) [6] Ring Gy, Bognár E, Dobránszky J, Ginsztler J, Major L: Mechanical Behaviours of Coronary Stents. Advances in Science and Technology. 49 (2006) [7] Szabó B, Bálint Pataki Zs, Ring Gy: Kobalt-króm ötvözetek orvostechnikai alkalmazása. BKL Kohászat 139 (2006:5) [8] Bálint-Pataki Zs, Bognár E, Ring Gy, Szabó B, Ginsztler J: Koszorúérsztentek vizsgálata. GÉP 2006/11 LVII évf., pp [9] Bognár E, Ring Gy, Dobránszky J: Investigation of coated coronary stents. Materials Science Forum (2007) [10] Ring Gy, Bognár E, Dobránszky J: Coronary Stents Materials and Examinations of Surface and Expansion Features. Materials Science Forum (2007) [11] Bognár E, Ring Gy, Marton H Zs, Dobránszky J: Development and Examination of Coated Coronary Stents. Anyagok Világa Materials World, 7 (2007:1) Bognar_Ring_Marton_Dobranszky.pdf [12] Bognár E, Ring Gy, Marton H Zs, Dobránszky J, Ginsztler J: Polyurethane coating on coronary stents. Key Engineering Materials (2007) [13] Bognár E, Ring Gy, Dobránszky J: Koszorúérsztentek bevonatainak tulajdonságai. Elektronikai technológia, Mikrotechnika. (under publ.) [14] Bognár E, Ring Gy, Balázs T, Dobránszky J: Investigation of Drug Eluting Stents. Materials Science Forum Vol. 589 (2008) pp (ISSN ) [15] Bognár E, Balázs T, Ring Gy, Szabó B, Nagy P: Stent Retention Measurement. Materials Science Forum 659 (2010) [16] Ring Gy, Bognár E, Dobránszky J: Fatigue testing of coronary stents. In: Hozman J, Kneo P (editors): IFMBE Proceedings, Vol. 11. Prague: IFMBE, ISSN Proceedings of the 3rd European Medical & Biological Engineering Conference EMBEC05. Prague, 8

10 Czech Republic, , [17] Bognár E, Ring Gy, Dobránszky J: Examinations of coated coronary stents expansion features and stability of the coatings. In: Hozman J, Kneo P (editors): IFMBE Proceedings, Vol. 11. Prague: IFMBE, ISSN Proceedings of the 3rd European Medical & Biological Engineering Conference EMBEC05. Prague, Czech Republic, November 2005, [18] Bognár E, Ring Gy, Dobránszky J: Bevonatos koszorúérsztentek vizsgálata és fejlesztése. XXIV. Neumann Kollokvium december Veszprém, allomanyok/bognare_1.nk2005.pdf ; március 2. [19] Ring Gy, Bognár E, Major L, Meszlényi Gy: Testing methods of coronary stents. In: Papp É, Mácsay I, Holubetz L (szerk.) Gépészet 2006 Proceedings of Fifth Conference on Mechanical Engineering, Budapest University of Technology and Economics, National Technical Information Centre and Library, Budapest, 2006, [20] Bognár E, Ring Gy, Dobránszky J, Ginsztler J: Examination of the coatings of coronary stents. In: Papp É, Mácsay I, Holubetz L (szerk.) Gépészet 2006 Proceedings of Fifth Conference on Mechanical Engineering, Budapest University of Technology and Economics, National Technical Information Centre and Library, Budapest, 2006, CD-ROM (ISBN ) [21] Bognár E, Ring Gy, Balázs T, Dobránszky J: Drug Distribution And Stent Retention of Drug Eluting Stents. Gépészet 2008, G-2008-N-12 n12.pdf 7 oldal (ISBN ) 9