International Circulation: You have previously mentioned that stroke is not an unmanageable complication for TAVR. How would do you go about managing the risk of stroke?
Dr. Martin Leon: “Not unmanageable” is a relative statement. In the early studies， there was a two-fold higher stroke in randomized surgical trials. This was with elderly and very sick patients， with a proto-type device that had not been used previously by anyone in 19 or the 22 sites enrolled in the study. That was our early data. When we looked at the continued access data， which comes after the randomized trial， the stroke rates in the later 2000 and more patients were much less. With more experience and better understanding of how to manage the native aortic valve with limited balloon dilatation and with lower profile devices， we think the intrinsic stroke rate will decrease. We also learned that， for example， adjunctive pharmacology and nuances in atrial fibrillation are other contributors to delayed stroke. We also think that a better understanding of how to manage those problems pharmacologically could also further reduce the stroke rates. Ultimately， there are devices called embolic protection devices that are being developed by multiple companies that are relatively easy to implant and deploy. These are temporary devices that can protect the brain during the procedure. For all of those reasons， the stroke issue is not one that I would ignore， but it is manageable in the context of evolutionary developments of technology in this space.
《国际循环》：您先前提到过，对TAVR，卒中并非难以控制的并发症。你会如何进行卒中风险管理？
Dr. Martin Leon： “非难以控制”是一种相对的说法。在早期研究中，随机手术试验中卒中风险升高2倍。这是对高龄和病情严重的患者，该研究在19或22个中心纳入患者，采用了以往未被任何人使用过的原型设备。那是我们的早期数据。当我们审阅来自随机试验后的连续访问数据，在后来的2000例以及更多患者中卒中发生率要低得多。随着经验的增加以及更好地了解如何以有限的球囊扩张和小尺寸鞘管来处理自体主动脉瓣，我们认为卒中发生率会降低。我们还了解到，辅助药物治疗和心房颤动对迟发卒中也有影响。如何使用药物更好应对这些问题还可以进一步降低卒中发生率。最后，多家公司正在开发易植入和展开的所谓栓子保护装置，这是在手术期间可以保护大脑的临时装置。基于上述所有这些原因，卒中问题是一个我不会忽略的问题，但在这一领域的技术发展的背景下，它是可以控制的。
International Circulation: Pharmacologically， do problems still exist in the management of stroke during TAVR?
Dr. Leon: We are definitely not there. We do not have a precise adjunctive pharmacological therapy. We used dual anti-platelet therapy， but we are sure of which are the best agents， or for how long to use them in these high-risk， elderly patients. A lot of these patients have atrial fibrillation and should be on warfarin or warfarin-like drugs. We are not sure if it should on that plus one or two other anti-platelet drugs. A European trial， pro TAVI， is a 2 by 2 factorial randomized study looking both embolic protection and different adjunctive pharmacology therapies to see if any combinations will have an important impact on stroke rates.
《国际循环》：从药物治疗方面看，在TAVR期间卒中的管理上是否仍然存在问题？
Dr. Leon： 我们绝对还没有达到那种境界。我们没有确切的辅助药物治疗。我们使用双重抗血小板治疗，但我们不确定哪种是最佳药物，或者在这些高风险的老年患者中要用多久。这些患者中很多有心房颤动，应该接受华法林或类似药物治疗。我们不确定是否应该接受这种药物再加一种或两种其他抗血小板药物治疗。欧洲试验PRO TAVI是一项2×2析因随机研究，观察栓子保护和不同的辅助药物治疗组合是否会对卒中发生率产生重要影响。
International Circulation: Could you please discuss some of the embolic protection devices?
Dr. Leon: These are filters and deflectors on small catheters that are placed in the arch and are there to protect the brain from any debris that may come off the valve as you are implanting the new one.
《国际循环》：能否请您讨论一下栓子保护装置？
Dr. Leon： 这些是置放于主动脉弓处的小型导管连接的过滤器和偏转器，用于在植入新瓣膜时保护大脑免于任何可能从瓣膜脱落的碎片。
International Circulation: Some presentations on these embolic protective devices seemed to be discussing whether or not they were working at all.
Dr. Leon: It is too soon to say. Early data is quietly suggesting that the rate of perfusion deficits from perfusion weighted MRI or high intensity transience from transcranial Doppler seem to be diminished when these devices are in place. But larger studies are needed and are being done now.
《国际循环》：一些有关这些栓子保护装置的介绍似乎在讨论他们是否发挥作用。
Dr. Leon：这还言之尚早。早期数据悄然提示，当这些装置就位时，灌注加权MRI的灌注缺损或经颅多普勒的高强度瞬时信号发生率似乎有所降低。但需要更大规模的研究，而且现在正在做这样的研究。
International Circulation: You’ve recently published about vascular complications. From that data or from your own experience， would you have any tips for practicing cardiologists?
Dr. Leon: That was the first generation system of very large-profile catheters. The reality is we have to respect the anatomy and respect the fact that careful， CT angiographic sizing of the peripheral vasculature is required to decide whether or not these patients undergo the procedure from a trans-femoral approach. Much better screening and using CT angiography is one issue. The second issue is low-profile devices. These are being developed rapidly right now. I believe with best clinical practices—careful screening， good technique， and low-profile devices—there is a small likelihood of increased vasculature complications in the future. There is a series coming out of Vancouver from John Webb， were he applied all of those criteria: complete percutaneous access enclosure， low-profile devices (with “pre-close”)， and careful vascular screening with CT angiography. His vasculature complication rate was literally a few percent in a consecutive series of patients. This suggests we will be able to overcome that problem with iterative technology， better technique， and better understandings.
《国际循环》： 您最近发表了有关血管并发症的文章。根据这些数据或者您自己的经验，你对执业心脏医师有何提示？
Dr. Leon：这是第一代极大尺寸的导管输送系统。现实是，我们必须尊重解剖，尊重下述事实，即需要谨慎的CT血管造影了解外周血管大小以决定这些患者是否接受经股动脉途径的手术。更好的筛查和利用CT血管造影是一个问题。第二个问题是小尺寸鞘管。这些装置目前正在迅速开发中。我认为，鉴于最佳临床实践--仔细的筛查、良好的技术和小尺寸鞘管--未来血管并发症增??加的可能性较小。有一个来自温哥华John Webb的系列研究，他应用了所有这些标准：完全的经皮入路闭合，小尺寸鞘管（伴有“预闭合”）和用CT血管造影进行仔细的血管筛查。在这个连续的系列患者中，其血管并发症发生率的确很小。这提示，借助更好的技术以及更好的了解，我们将能够克服这个问题。
International Circulation: For physicians new to TAVR， what are the best ways to predict patient response?
Dr. Leon: There are a lot of things that we are considering. There are few definitive scores that proven helpful. There was score from a German registry， called GARY， which was a way of looking at a variety of risk factors to see if the risk algorithms could better predict outcomes than the conventional scores， which are either STS or EuroSCORE. We are still struggling with that. We are the midst of study of over 8000 patients. This is a collaboration between the United States and Europe， with both the PARTNER and SOURCE data and some high-brow bio-statisticians to come up with a TAVI score to predict patient outcomes. This way， we can better tell our patients what our expectation is with regard to their likelihood of improvement. We have learned some things about important criteria， for instance， gender. Women do much better with this procedure than surgery. We believe that is one patient population group that tends to do better if they are high-risk. We have also learned that if you are too much in the way of comorbidities—a high STS score， extremely frailty， evidence of dementia—patients may fall into a category that we call “futility.” In this case， it may not be a good idea to perform this procedure because there are many issues beyond the aortic stenosis. To invest all the effort in a procedure is not going to make the patient feel better because of other co-morbid situations.
《国际循环》：对新接触TAVR的医师，预测患者反应的最佳方法是什么？
Dr. Leon：有很多我们正在考虑的事情。明确证明有帮助的评分很少。有来自德国注册研究的评分系统－GARY，该评分考虑各种危险因素以观察风险算法是否较传统评分STS或者EuroSCORE评分更好地预测结果。在这一点上我们仍然在努力。我们正在进行一项包含8000多例患者的研究。这是美国和欧洲之间的合作，合并了PARTNER和SOURCE的数据，由一些高水平生物统计学家共聚一堂形成一项TAVI评分来预测患者结果。通过这种方式，我们可以更好地告诉我们的患者，就其改善的可能性而言，我们的预期是什么。有关重要标准，我们已经有所了解，例如，性别。女性采用这种介入手术比外科手术要好得多。我们认为，如果他们是高危患者，那么这是一个往往会做得更好的患者群体。我们还了解到，如果你有太多合并症--高STS评分，极其脆弱，痴呆症患者的证据可能会归入一个我们称之为“无效”的类别。在这种情况下，进行这种手术可能不是一个好主意，因为在主动脉瓣狭窄之外还有许多问题。由于其他并存疾病，将所有的努力都投入在手术上并不会使患者感觉更好。
International Circulation: How often or how many patients do you think fit into both “appropriate for TAVR” and “futility” groups?
Dr. Leon: That is difficult to estimate. Let us look at the penetration of TAVI in Europe. In the high-volume centers， about half the aortic valve replacements are being done with TAVR. If you look at 11 European countries the penetration rate for appropriate patients is about 25% of patients that could be candidates for valve replacement: people over the age of 75， with severe aortic stenosis who are symptomatic. That is increased by a factor of 5 over the last several years. That is rapidly increasing. There are two studies right now， one is called PARTNER2A and the other is SURTAVI which monitor moderate risk patients. The inoperable patients probably represent 10% of the AS patient cohort， another 10% would be the upper decile of high-risk， but operable patients， then there is another 25% of patients that are in the moderate risk， and then there are low risk patients. We would not recommend this for low-risk patients. For moderate-risk patients， there is enough equipoise to suggest that a randomized trial is appropriate. That is what we are doing. We have already enrolled close to 800 patients in the PARTNER2A study.
《国际循环》：你认为有多少患者既可纳入“适合TAVR”又可纳入“无效”群体？
Dr. Leon：这是难以估量的。让我们来看看TAVI在欧洲的普及。在高容量中心，大约一半的主动脉瓣置换术是采用TAVR做的。在11个欧洲国家，合适患者的普及率为瓣膜置换术候选患者（75岁以上者，有症状的重度主动脉瓣狭窄患者）的约25％。也就是说在过去几年期间增加了5倍，即迅速增加。现在有两项研究，一项称为PARTNER2A，另一项是SURTAVI，后者监测的是中危患者。不能手术的患者大概占AS患者队列的10％，另外10％是属于上十分位数的高危但可手术患者，有另外25％的患者是中危，然后还有低危患者。对低危患者，我们不推荐这个。对中危患者，有足够的证据提示，进行一项随机试验是适合的。这也正是我们所在做的事情。我们在PARTNER2A研究中已经纳入了近800例患者。
International Circulation: There was an article from Belgium discussing the economic feasibility of TAVI in high-risk groups. Could you please comment on this article?
Dr. Leon: It was two economists and it was a controversial article with much confusing data. Belgium is an interesting country. They have markedly more sites performing TAVI per unit population than any other country in Europe. They also have by far the fewest number of cases done per site of any country in Europe. It is not clear what their points are. The reality is there are careful cost-effectiveness studies in progress. One that we did is part of the PARTNER trial with David Cohen. Both inoperable and high-risk patients clearly demonstrate cost-effectiveness. Another confirmation came from two groups in the UK—just presented at London Valves Meeting—again looked at inoperable and high-risk patients and again showed that it is cost-effective technology. I do not know how to react to the articles contention that it does not provide sufficient value or that TAVI is too risky. This is a life saving procedure. You do not need to treat many patients to save a life. There are very few things we do in medicine that allow us to say that. One of the problems is that patients who are not treated die quickly. The problem with cost-effectiveness studies in that population is that it is very cheap if you die quickly. These elderly patients with comorbidities are expensive to keep alive， independent of TAVR. This needs to be viewed from a societal perspective.
《国际循环》：有一篇来自比利时的文章讨论了在高危人群中TAVI的经济可行性。您能否对这篇文章进行评论？
Dr. Leon：这是两位经济学家，这是一篇有争议的文章，数据非常混乱。比利时是一个有趣的国家。与任何其他欧洲国家相比，他们每单位人口开展TAVI的中心显著较多。然而，到目前为止，在欧洲任何一个国家中，他们每个中心的病例数量是最少的。尚不清楚他们的观点是什么。现实是，周密设计的成本效益研究正在进行中。其中之一是David Cohen所做的PARTNER试验的一部分。不能手术和高危患者都明确证实了成本效益。另一个确认来自英国的两个群体--刚在伦敦瓣膜会议上汇报过--还是观察的不能手术和高危的患者，且再次证明它是具有成本效益的技术。对文章争论，我不知道如何作出反应，它并未提供足够的价值或者TAVI太过危险。这是一个挽救生命的手术。您不需要治疗很多患者就可以挽救一个生命。在医学领域，我们能够这样说的事情非常少。其中一个问题是，未治疗的患者很快死亡。这一人群中成本效益研究的问题是，如果很快死亡那么花费自然非常少。这些有合并症的老年患者活着的代价是昂贵的，独立于TAVR之外。这需要从社会的角度来看待。
International Circulation: Do you believe TAVR will move on to moderate risk patients?
Dr. Leon: I think that we need to do the studies， look at the data， and see if the stroke rates are going down， as the primary endpoint is death from stroke. If TAVI is equivalent to surgery then we can discuss whether that will be an alternative for patients. Surgery for patients with AS is the best operation we do in cardiovascular medicine. I would never say that surgery is not a good thing. There will be a role for TAVR in the armamentarium of physicians and we are going to need to find that niche. As devices get better， as studies generate more data， we will try to understand whether or not it should drift to intermediate risk categories and other categories we are looking at， including patients with coronary disease， patients with failed bioprosthetic valves. There are many places where this technology can potentially provide an alternative benefit for patients.
《国际循环》：你认为TAVR会继续拓展到中危患者吗？
Dr. Leon：我认为，我们需要进行研究，看数据，观察卒中发生率是否在降低，因为主要终点是因卒中死亡。TAVI是否与外科手术相等，然后我们就可以讨论这对患者而言是否是一种替代选择。 对AS患者来说，外科手??术是我们在心血管医学中所能做的最好的操作。我从来不会说，手术不是一件好事。在医师的医疗设备中，TAVR将会发挥一定作用，我们需要找到其合适的位置。随着装置变得越来越好，随着研究产生更多的数据，我们会试着去了解它是否应当拓展到我们正在观察的中危类别和其他类别，包括冠心病患者，生物瓣膜失败的患者。在许多地方，这种技术可能为患者提供一种替代益处。
International Circulation: Are you worried that doctors may be being too forward and there may be a risk creep?
Dr. Leon: People have talked about that. There may be a risk creep in Germany， but talking to the doctors there， it turns out that it is a matter of judgment. They feel strongly that patients in their late 80s do better in non-surgical procedures and that the recovery is faster. We are not going to be able to show that their mortality is benefited， but the fact that they can be out of the hospital in days and back to a viable lifestyle in a week or two is meaningful for these patients. Some of us feel we should elevate some of the soft secondary endpoints and how they should be meaningfully incorporated into how people use this technology.
《国际循环》：你是否担心医生可能太过激进，有可能是一种风险蠕变？
Dr. Leon：人们已经讨论过这个问题。在德国有可能是一种风险蠕变，但与那里的医生探讨发现，结果证明这是一个判断的问题。他们强烈地认为，接近90岁的患者做非外科手术会更好，且恢复速度更快。我们不能证明其死亡率受益，但他们几天内就可以出院，一周或两周内就可以回到可以自理的生活方式的事实对这些患者来说是有意义的。我们中的一些人认为，我们应该提升一些软次要终点，在人们如何使用这项技术中这些软终点是有意义的。
International Circulation: What about for patients who refuse surgery?
Dr. Leon:I think that if the patient is 75 with no comorbidities and a 1% risk of serious problems during surgery， I would convince the patient that it would be a terrible mistake for them not to have surgery. If that same patient is in their upper 80s， they have one or two comorbidities， and even if their risk score does not put them in the high-risk group. To me， that is a different structure.
《国际循环》： 对拒绝外科手术的患者，如何处理？
Dr. Leon：我认为，如果患者是75岁，没有合并症且术中严重问题的风险为1％，我会说服患者，对他们来说不接受手术治疗将会是一个可怕的错误。如果同样的患者已接近90岁，有一种或两种合并症，即使他们的风险评分并未将他们放在高危群体中，对我来说，这也是不同的结构体。
International Circulation: Could you discuss the idea of a heart team?
Dr. Leon: In the real world， everything is done under the aegis of physicians that speak together and with the patient to prevent all sides of the argument. The heart team is fundamental. One cannot get reimbursed in the US unless you have a heart team. One cannot even be trained or certified as a TAVR site unless you have a functioning heart team. In fact， you cannot get reimbursed by CMS unless you have a surgeon and an interventionist in the room for every procedure.
《国际循环》： 您能讨论一下心脏团队的想法吗？
Dr. Leon：在真实世界中，一切都是在医师的主持下进行，一起与患者商量以预防所有方面的争论。心脏团队是基础。在美国，如果没有心脏团队，你就不能获得保险公司或政府的支付。只有你有一个正常运作的心脏团队，你才能接受培训或被认证为TAVR中心。事实上，你不能得到CMS的赔偿，除非每个过程都有一位外科医生和一位介入医生在位。
[下一页] [1] [2] [3] [4] [5] [6]