1、HANCOCK II,第二代生物瓣技术,Carpentier-Edwards Perimount Bioprostheses,Magna valve PERIMOUNT valve,(CEP),保存方法：,在压力下应用戊二醛 ，促进胶原纤维之间的交联胶原纤维交联可避免胶原纤维断裂胶原纤维断裂最终可以导致钙化形成，进而导致瓣膜失效,生理固定对Valsalva窦和瓣叶功能的作用,影响血流动力学和耐久性,减轻 生物机械性 失效,新鲜瓣叶,戊二醛固定方法的进步,放射显像：取出的猪生物瓣,Lentz D et al. Inhibition of Mineralization of Glutaraldeh
2、yde-Fixed Hancock Bioprosthetic Heart Valves. In: Cohn LH, Galucci V (ed) Cardiac Bioprostheses, Proceedings of the 2nd Intl Symp. York Med Books, NY 1982 306-19,T6 处理后（左） 未处理（右）,流出道面。在植入4个月后取出的 Hancock瓣膜。 标准瓣膜 (right) ，和T6处理后的 (left).,Amino group,AOA 法至少从三个方面减少钙化:降低了钙离子弥散到组织中的速度在戊二醛固定的组织上形成了性能良好且耐久
3、性强的结合。（共价结合）可能可以洗脱一些脂质,来自天然产生带油酸,AOA-treated,Non-treated,Duarte; Emory University, Atlanta, GA,放射显像提示了钙化组织的位置,AOA处理的瓣膜及对照组的大体外观,Mosaic 瓣羊研究: 植入5个月后取出：,第一代支架HK I聚丙烯,第二代支架HKII 聚甲醛支架变薄圆形凸起侧高降低2 mm X线可探查的环及孔,瓣环下缝合圈和瓣环下瓣架,瓣环上缝合圈和瓣环下瓣架,瓣环上缝合圈 和瓣环上瓣架,瓣环内人工瓣,真正的瓣环上 (Supra-X),Supra-X 真正的环上环外瓣,Supra X: 瓣孔面积,瓣
4、架在孔内孔径相当于瓣架内径,瓣环内没有任何阻碍中央孔和瓣环面积匹配需要全新的测瓣概念,瓣环支架孔面积,Supra-X,瓣环上缝合环,CEP,HK II, Mosaic,瓣膜开闭更接近真实人体瓣膜,拼合式生物瓣（牛心包瓣或猪瓣膜等）,Hancock II,二尖瓣位 - 安全、迅速、不挂线,主动脉瓣位,全球专利CINCHTM旋转收缩瓣角机制,其他产品,Hancock II 二尖瓣,缝合圈与支架均置于环间:,缝合圈置于环上支架置于环间:,真正的环上瓣(Supra-X):缝合圈与支架均置于环上的,测瓣: 真正的环上瓣HKII vs 环内瓣CEP,Hancock II 测瓣器底部=Hancock II
5、生物瓣的内径=病人瓣环内径凸起=代表瓣膜支架柱的大小和位置，有助于确定正确植入方位,CEP的环内瓣测瓣器,HKII 侧高,21mm,19.1mm,21mm,19.1mm,21mm,Hancock II 内径20.5mm,23mm,HKII瓣号=支架外径HKII 内径=病人瓣环内径23mm Hancock II,CEP瓣号=CEP支架外径=病人瓣环内径 21mm CEP,CEP 外径21mm,病人瓣环21mm,性能对比,组成设计三个瓣叶都是无冠瓣瓣叶低压固定戊二醛 1mmHg接合处有牛心包保护减少瓣叶在织物上的磨损 Celcon 支架 比乙缩醛均聚物（ HK II 支架 ）的抗张强度小，柔软性差
6、无抗钙化处理,Biocor 生物瓣,连接处犹打结般，挡在流出道，跨瓣压差升高薄弱环节，是血栓形成和钙化的潜在发生位点,Biocor 主动脉瓣,Epic,Linx 处理 仅采用乙醇 与Biocor相比，并没有减少钙化一项20周的利用小羊二尖瓣置换模型进行的研究，用于研究( Biocor vs Epic )的安全性和有效性，以及银的释放速率和营养不良性钙化的程度结果：20周的羊模型无法检测出Epic和Biocor生物瓣之间钙沉积的差别*无有效远期数据,* Langanki et al; Journal of Heart Valve Disease : 1998 Nov;7(6):633-8.,SJ
7、说他们的侧瓣高只有11mm,但是过低的侧瓣高=更差的血流动力学,Hancock II,侧高过低的瓣膜,(mmHg),跨瓣压差,芬兰心脏中心因为高跨瓣压差停止使用Biocor 转用低跨瓣压差的Hancock II,Myken P等 St. Jude Medical Biocor 猪心瓣15年随访结果 “心脏瓣膜疾病杂志” 2000年第9卷415-422页,高跨瓣压差导致过早衰败！,Biocor与Hancock II 15年瓣膜结构衰败率比较,Biocor - Kirali,Biocor - Myken,HK II,HK II,1. Myken P, Bech-Hanssen, Phipps B,
8、 Caidahl K. Fifteen Years Follow Up with the St. Jude Medical Biocor Porcine Bioprosthesis. J Heart Valve Dis 2000; 9: 415-4222. David et. al; Later results of heart valve replacement with Hancock II Bioprosthesis; The Journal of Thoracic and Cardiovascular Surgery: Vol 121, Number 2 Pg 268-278 3. K
9、irali et al; Fifteen year clinical experience with the Biocor Porcine Bioprosthesis in the Mitral position; Ann Thoracic Surgery 2001; 71:811-815,二尖瓣,主动脉瓣,Epic是什么?,SJM Epic 没有长期或短期的临床研究证据！ Linx 抗钙化处理可能使血流动力学表现进一步降低，因为酒精可以逐渐使组织干燥和变硬。 (Linx 使用的是95%的酒精） 研究未能证实经过 Linx 处理的瓣膜比没有处理过的Biocor瓣膜具有任何优势。（同时也没有人类
10、研究证据）,Epic 只不过是额外增加了Linx处理的Biocor瓣,ACC AHA 指南对生物瓣使用的建议：,AVR: Patients 65:With discussion with surgeon about strong risk of reoperation versus the risk of anticoagulationWomen of child bearing ageMVR: Patients 65 who:Are in sinus rhythm andWith discussion with surgeon about strong risk of reoperation
11、 versus the risk of anticoagulationAny age:Patients who will not or can not take wafarin anticoagulation,病人年纪越大，耐久性越好,Patient ages,不同病人年龄的换瓣选择,Mechanical,Tissue,Patient Age,Average patient age,Z. Al Halees, B Gometza, A Al Sanel, CM Duran Behavior of the Hancock II Bioprosthesis in Young Population.
12、 World Symposium on Heart Valve Disease, 1999 London. From the King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia and International Heart Institute of Montana foundation, Missoula, Montana, USA,HANCOCK II,Performance in Patients Ages 11-40,Benefits of Physiologic Fixation,Phys
13、iologic Fixation,Pressure Fixation,Hinge site,Physiologic Fixation,Supra-X Positioning,Supra-X positioning ensures the Mosaic bioprosthesis is seated supra-annularly while aligning the internal diameter of the valve with the patients annulus No intra-annular component Increases area available to flo
14、w,Intra-annular sewing ring with intra-annular valve,Supra-annular sewing ring with intra-annular valve,True Supra-annular (Supra-X):Supra-annular sewing ring with supra-annular valve,Intra-annular valves,Supra-annular valve,Supra-X Positioning,经导管肺动脉瓣膜,Philippe Bonhofer - 90年代后期可用 - 首次在人类应用,可以为婴儿赢得
15、时间，可以延后接受外科手术的时间,上腔静脉路线,从10月1日起已经超过800例病人,经导管主动脉瓣膜置换,CoreValve . 可能还有更多 !,Cribier, Edwards,REFERENCES1 Riess, FC et al., Hemodynamic Performance and Clinical Follow-up of the Medtronic Mosaic Bioprosthesis up to 12 Years. ABSTRACT, presented at the SHVD, New York, NY, 2007. Banbury MK et al., Long-T
16、erm Results of the Carpentier-Edwards Pericardial Aortic Valve: A 12-Year Follow-Up. Ann Thorac Surg 1998;66:S736.Banbury MK et al., Age and Valve Size Effect on the Long-Term Durability of the Carpentier-Edwards Aortic Pericardial Bioprosthesis. Ann Thorac Surg 2001;72:753-7.,Confidential,Mitral Re
17、gurgitation,Possible Reasons,It has a hole in itUnequal leaflet elasticityLow stent postsCauses leaflet coaptation zone to be very small,Triangle of leak,CEP Valve,Sizing and Implantation,SizingImplantInflow View,Hancock II,CEP,Stent ID,Stent ID,Stent OD,AnnulusStentOrifice Area,Not all sizers are t
18、he same,Not all sizers are the same,Upsize,Plastic is more Flexible than Metal,Hancock II valvePlastic ( acetal homopolymer ) stent. Low memory and flexible,CEPMetal stentMetal has memory and can break,Plastic,Metal,VS,CEP IFU : Due to the relative flexibility of the frame, care must be exercised to
19、 prevent folding or deformation of the stent, that might lead to regurgitation, altered hemodynamics, and/or leaflet disruption rendering the valve incompetent.,Ease of Implant Aortic Position: CINCHTM Holder Profile Comparison,23 mm Carpentier Edwards Perimount ,23 mm HII with the CINCHTM,Ease of I
20、mplant : CINCHTM In Aorta Profile Comparison,Hemodynamic Comparison EOA,Hemodynamic ComparisonMean Gradient Mosaic,Hemodynamic ComparisonMean Gradient CEP,Weighted average of Mean Gradient,PORCINE vs PORCINE? What makes a difference?,SJM Biocor Stented Tissue Valve,Biocor is a registered trademark o
21、f St. Jude Medical Inc.,Biocor,Epic,History 1978 Biocor porcine valve developed by Dr. Mario Vrandecic in Brazil. 1982 Biocor valve released. 1996 September: SJM acquires Biocor tissue valve company. 1998 Biocor receives CE Mark. 2003 US clinical study begins on the SJM Epic with Linx AC 2003 Europe
22、an launch of the Epic Supra 2004 First North American implant of its SJM Epic Supra valve. 2005 August 8th Biocor approved for sale in United States.,Valve Feature Comparison,Composite designThree non-coronary cuspsLow pressure fixationGlutaraldehyde 1mmHgPericardial shield on the outflow edge reduc
23、e leaflet abrasion against fabricCelcon stent lower tensile strength and less flexible than acetal homopolymer (HK II stent). No anti-calcification treatment,Biocor bioprostheses,Epic,Linx treatment just ethanol no reduction in calcification vs BiocorA 20-week juvenile sheep mitral valve implant mod
24、el was used to determine safety and efficacy of the device ( Biocor vs Epic ), as well as the rate of silver release and degree of dystrophic calcification Results : the 20-week sheep model unable to detect differences in calcium accumulation between the Epic and the Biocor *No long-term data availa
25、ble,* Langanki et al; Journal of Heart Valve Disease : 1998 Nov;7(6):633-8.,Biocor How is it produced ?,Hemodynamics,Not all porcine valves are the same - Biocor Lower Profile, Worse Hemodynamics,FeaturesProfile: Leaflets Are STUFFED into stents that are too smallHigher leaflet stressesLeaflet protr
26、usion,Pericardial shield obstructing flow area. Shield inhibits leaflets from opening fully.,Biocor Aortic Valve,Stress folds are evident radiating from the base of the commisures as well as coaptation mis-alignment.,Biocor,HKII, Mosaic,Acceptable Hemodynamics?,Mykn PS et al., LONG-TERM DOPPLER ECHO
27、CARDIOGRAPHIC RESULTS OF AORTIC OR MITRAL VALVE REPLACEMENT WITH BIOCOR PORCINE BIOPROSTHESIS. J Thorac Cardiovasc Surg 1998;116:599-608.,Would gradients of up to 60 mmHg be acceptable with a Mosaic or Hancock II?,Durability,Not all porcine valves are the same - Another way to look at the data,Compa
28、rison of SVD between Biocor and Hancock II at 15 yrs,Biocor - Kirali,Biocor - Myken,HK II,HK II,1. Myken P, Bech-Hanssen, Phipps B, Caidahl K. Fifteen Years Follow Up with the St. Jude Medical Biocor Porcine Bioprosthesis. J Heart Valve Dis 2000; 9: 415-4222. David et. al; Later results of heart val
29、ve replacement with Hancock II Bioprosthesis; The Journal of Thoracic and Cardiovascular Surgery: Vol 121, Number 2 Pg 268-278 3. Kirali et al; Fifteen year clinical experience with the Biocor Porcine Bioprosthesis in the Mitral position; Ann Thoracic Surgery 2001; 71:811-815,VS,Clinical Comparison,
30、Comparison of SVD between Biocor and Hancock II at 20 yrs,Implantability,Not all porcine valves are the same - The Cinch Makes A Difference,The Biocor plastic stent is less flexible than the HKII stent. The Biocor stent post are unable to deflect as well as the HKII stent post. The Biocor has a bulk
31、y holder which makes it difficult for the surgeon to visualize and to secure the knots during the procedure,Biocor,Hancock II,Theory: Reduces glutaraldehyde toxicity Removes cholesterol and lipids Reduces uptake of lipids from the patient into the prosthesis Testing: Connolly, Levy RJ et al. J Heart
32、 Valve Dis 2004;13(3):487-93. Vyavahare, Levy RJ et al. J Biomed Mater Res 1998 40;577585. Flameng, et al. Ann Thorac Surg 2001;71:S401-5. Langanki, et al. J Heart Valve Dis 1998;7:633-638. Shoen, Levy RJ et al. Ann Thorac Surg 2005;79:1072 80).,Linx Technology,What we know about Linx?,The Linx anti
33、calcification treatment is a simple 95% ethanol treatment. The Linx treatment has been developed by Dr. Robert Levy at the University of Michigan and is licensed by SJM.21-day rat subdermal tests were performed (No human studies!)20-day juvenile sheep studies showed no difference than untreated Bioc
34、or samples.Studies found abnormally high amounts of cuspal hematomas.,Proof Source?,Vyavahare 2000 Paper,“Our initial studies explored ethanol pretreatment, but only after glutaraldehyde fixation. We also did not examine questions of storage in glutaraldehyde solution after ethanol pretreament. “In
35、conclusion, glutaraldehyde storage following ethanol pretreatment of glutaraldehyde-fixed bioprosthetic heart valves negates inhibition of calcification, and would appear to be contraindicated in the fabrication of such valves for clinical use.”,Vyavahare, et al. Prevention of glutaraldehyde-fixed b
36、ioprosthetic heart valve calcification by alcohol pretreatment: further mechanistic studies. J Heart Val Dis 2000:9(4);561-6.,Where does that leave Epic?,There is no long or short-term clinical data available on the SJM Epic ! Linx anticalcification treatment might further reduce hemodynamic perform
37、ance since alcohol generally dries and stiffens the tissue. (Linx is 95% ethanol). Studies have not been able to prove that valves treated with Linx performed any better than non-treated Biocor valves (Nor any human studies).,Epic is simply the Biocor valve with the addition of Linx,SJM说生物瓣侧瓣越低越好，真是
38、这样吗？,生物瓣Newsletter,两种不同的猪主动脉瓣,完整猪主动脉瓣,瓣叶组合瓣,完整的猪主动脉瓣和人主动脉瓣膜结构对比,Data Source: FDA Approved Instructions for Use.,主动脉血流动力学,FDA审批IFU数据：术后一年平均跨瓣压差比较,侧瓣越低，瓣叶张力越大,20年生存率和耐久性的比较,| MDT Confidential,86,总结,HKII 采用猪的完整主动脉瓣，解剖更加接近人体瓣膜结构，瓣叶运动更符合生理情况Biocor降低了侧瓣高度，导致瓣叶无法完全打开，牺牲了血液动力学生物瓣侧瓣越低，瓣叶承受的张力越大，耐久性下降。而耐久性是生物
39、瓣最重要的考虑因素美敦力的CINCH 技术，能有效地避免二尖瓣植入时造成的心肌损伤。只要植入角度符合要求，左室流出道受阻极少发生。,竞争对手临床实验比较,Freedom From SVD 比较,耐久性总结：60岁及以上患者 FFSVD 85%60岁及以上患者 AVR FFSVD 88%65岁及以上患者 AVR FFSVD 97%,指南建议年龄生物瓣患者首选！,患者生存率,生存率为什么重要？,一切数据结果的基础！,免予结构性衰败率FFSVD,60-70岁患者 植入20年总体FFSVD 85%主动脉 FFSVD 88%,60-70岁患者 植入20年总体FFRSVD 90%主动脉 FFRSVD 92
40、%,瓣膜的分类,HKII 和Perimount 瓣叶重叠区域对比,HKII,Perimount,Deeper coaptation,Shallow coaptation,Medtronic Mosaic Aortic and Mitral Bioprosthesis: Fifteen Year Clinical Compendium. Medtronic, Inc. 2012. Carlo Valfre etal ,The fate of Hancock II porcine valve recipients 25 years after implant. European Journal o
41、f Cardio-thoracic Surgery 38 (2010) 141146Banbury MK. et al., Age and Valve Size Effect on the Long-Term Durability of the Carpentier-Edwards Aortic pericardial Bioprosthesis. Ann Thorac Surg 2001;72-753-7. Carpentier-Edwards PERIMOUNT Mitral Pericardial Bioprosthesis Communiqu, Model 6900, 2003 Edw
42、ards Lifesciences LLC.,Mosaic是二尖瓣耐久性最好的生物瓣,生物瓣衰败原因,物理性因素：血流冲击撕裂等,压力,组织原因,瓣膜结构衰败,化学性因素：固定剂钙化,Schoen F, Levy R. Tissue Heart Valves: Current Challenges and Future Research Perspectives. J Biomed Mater Res, 47, 439-465, 1999,如何对抗两种瓣膜失效原因？, 改进瓣架设计 (生物机械性) 改进戊二醛处理和压力固定技术 (生物机械性） 使用抗钙化剂 (生物化学性),CINCH II 有
43、效的保护心室纵向环,PERIMOUNT THEON,MODEL 6900PTFX,MAGNA MITRAL EASE,MODEL 7300TFX,ThermaFix process*BioengineeredFlexible CoCr alloy stentPericardial leaflets,ThermaFix process*BioengineeredFlexible CoCr alloy stentPericardial leaflets,Supra-annular designLowest profile Ease of implant,Edwards Mitral,Edwards
44、 宣传卖点,经过大量临床数据验证的血液动力学EOA &平均跨瓣压差为耐久性而设计独特的ThermaFix工艺提高了瓣膜的长期性能安全易于植入Tricentrix传送系统,St. Jude Medical Biocor & Epic Stented Tissue Valves,Biocor特点,三片独立瓣膜（无冠瓣）,组合瓣,FlexFit System,Linx AC去钙化功能,瓣架: 由于支架过低，留给瓣叶的空间过于狭小 瓣叶承受更高压力 瓣叶更突出，无法保持自然形态,低瓣架设计与血流动力学,St. Jude Biocor 带支架生物瓣,Biocor is a registered trad
45、emark of St. Jude Medical Inc.,Biocor,Epic,复合瓣叶设计由三片独立裁剪的无差异瓣叶组成低压固定技术固定压力小于 1mmHgGlutaraldehyde 1mmHg流出道瓣脚边缘心包保护 减少瓣叶与纺织物之间的摩擦Celcon 材料支架 低强度，低弹性支架（与HKII支架相比较）无抗钙化处理,Biocor人工生物瓣膜,Epic 人工生物瓣膜,Linx 抗钙化试剂主要成分 无水酒精 没有带来比Biocor更好的抗钙化效果一项针对Biocor 和EPIC抗钙化效果试验的结果显示，在小羊体内植入Biocor和EPIC二尖瓣，20周后，EPIC在钙离子沉积效果上
46、，与Biocor并无差异！缺乏长期临床数据支持,* Langanki et al; Journal of Heart Valve Disease : 1998 Nov;7(6):633-8.,抗钙化能力:6周之后,5 /5Magna 发生钙化中心留有缝隙 1 / 5 Mosaic 发生钙化,a b c d e f g,Opening and Closing kinematics: Magna (top) and Mosaic (bottom),Calcium,扩大1个瓣号,Increase in gradient observed when inflow of valve is obstruc
47、ted,新测瓣器使用步骤,第一步: 使用测瓣器桶端测量瓣膜大小,* If the potential exists for (a) valve prosthesis interference with coronary ostia, (b) tissue obstruction to valve prosthesis inflow, or (c) deformation of the valve prosthesis stent, consider reorientation of the valve, selecting a smaller valve size, or addressing the obstruction or interference surgically.,此例显示，25mm瓣膜对23mm瓣膜的比较,新Mosaic 测瓣器,Replica End,Barrel End,DO NOT COPY NOT FOR DISTRIBUTION,The closing problem(Stroke volume 80 ml / 6 weeks) 4 l / 40 bpm (high stroke volume of 80 ml),
