Aneurysm, Dissecting

ORLANDO – At HIMSS24 on Tuesday, Dr. John Halamka, president of Mayo Clinic Platform, offered a frank discussion about the substantial potential benefits – and very real potential for harm – in both predictive and generative artificial intelligence used in clinical settings. Healthcare AI has a credibility problem , he said. Mostly because the models so often lack transparency and accountability. "Do you have any idea what training data was used on the algorithm, predictive or generative, you're using now?" Halamka asked. "Is the result of that predictive algorithm consistent and reliable? Has it been tested in a clinical trial?" The goal, he said, is to figure out some strategies so "the AI future we all want is as safe as we all need." It starts with good data, of course. And that's easier discussed than achieved. "All algorithms are trained on data," said Halamka. "And the data that we use must be curated, normalized. We must understand who gathered it and for what purpose – that part is actually pretty tough." For instance, "I don't know if any of you have actually studied the data integrity of your electronic health record systems, and your databases and your institutions, but you will actually find things like social determinants of health are poorly gathered, poorly representative," he explained. "They're sparse data, and they may not actually reflect reality. So if you use social determinants of health for any of these algorithms, you're very likely to get a highly biased result." More questions to be answered: "Who is presenting that data to you? Your providers? Your patients? Is it coming from telemetry? Is it coming from automated systems that extract metadata from images?" Once those questions are answered satisfactorily, that you've made sure the data has been gathered in a comprehensive enough fashion to develop the algorithm you want, then it's just a question of identifying potential biases and mitigating them. Easy enough, right? "In the dataset that you have, what are the multimodal data elements? Just patient registration is probably not sufficient to create an AI model. Do you have such things as text, the notes, the history and physical [exam], the operative note, the diagnostic information? Do you have images? Do you have telemetry? Do you have genomics? Digital pathology? That is going to give you a sense of data depth – multiple different kinds of data, which are probably going to be used increasingly as we develop different algorithms that look beyond just structured and unstructured data." Then it's time to think about data breadth. "How many patients do you have? I talked to several colleagues internationally that say, well, we have a registry of 5,000 patients, and we're going to develop AI on that registry. Well, 5,000 is probably not breadth enough to give you a highly resilient model." And what about "heterogeneity or spread?" Halamka asked. "Mayo has 11.2 million patients in Arizona, Florida, Minnesota and internationally. But does it offer a representative data of France, or a representative Nordic population?" As he sees it, "any dataset from any one institution is probably going to lack the spread to create algorithms that can be globally applied," said Halamka. In fact, you could probably argue there is no one who can create an unbiased algorithm developed in one geography that will work in another geography seamlessly. What that implies, he said, is you need a global network of federated participants that will help with model creation and model testing and local tuning if we're going to deliver the AI result we want on a global basis." On that front, one of the biggest challenges is that "not every country on the planet has fully digitized records," said Halamka, who was recently in Davos, Switzerland for the World Economic Forum. "Why haven't we created an amazing AI model in Switzerland?" he asked. "Well, Switzerland has extremely good chocolate – and extremely bad electronic health records. And about 90% of the data of Switzerland is on paper." But even with good digitized data. And even after accounting for that data's depth, breadth and the spread, there are still other questions to consider. For instance, what data should be included in the model? "If you want a fair, appropriate, valid, effective and safe algorithm, should you use race ethnicity as an input to your AI model? The answer is to be really careful with doing that, because it may very well bias the model in ways you don't want," said Halamka. "If there was some sort of biological reason to have race ethnicity as a data element, OK, maybe it's helpful. But if it's really not related to a disease state or an outcome you're predicting, you're going to find – and I'm sure you've all read the literature about overtreatment, undertreatment, overdiagnosis – these kinds of problems. So you have to be very careful when you decide to build the model, what data to include." Even more steps: "Then, once you have the model, you need to test it on data that's not the development set, and that may be a segregated data set in your organization, or maybe another organization in your region or around the world. And the question I would ask you all is, what do you measure? How do you evaluate a model to make sure that it is fair? What does it mean to be fair?" Halamka has been working for some time with the Coalition for Health AI, which was founded with the idea that, "if we're going to define what it means to be fair, or effective, or safe, that we're going to have to do it as a community." CHAI started with just six organizations. Today, it's got 1,500 members from around the world, including all the big tech organizations, academic medical centers, regional healthcare systems payers, pharma and government. "You now have a public private organization capable of working as a community to define what it means to be fair, how you should measure what is a testing and evaluation framework, so we can create data cards, what data went into the system and model cards, how do they perform?" It's a fact that every algorithm will have some sort of inherent bias, said Halamka. That's why "Mayo has an assurance lab, and we test commercial algorithms and self-developed algorithms," he said. "And what you do is you identify the bias and then you mitigate it. It can be mitigated by returning the algorithm to different kinds of data, or just an understanding that the algorithm can't be completely fair for all patients. You just have to be exceedingly careful where and how you use it. "For example, Mayo has a wonderful cardiology algorithm that will predict cardiac mortality, and it has incredible predictive, positive predictive value for a body mass index that is low and a really not good performance for a body mass index that is high. So is it ethical to use that algorithm? Well, yes, on people whose body mass index is low, and you just need to understand that bias and use it appropriately." Halamka noted that the Coalition for Health AI has created an extensive series of metrics and artifacts and processes – available at CoalitionforHealthAI.org . "They're all for free. They're international. They're for download." Over the next few months, CHAI "will be turning its attention to a lot of generative AI topics," he said. "Because generative AI evaluation is harder. With predictive models, "I can understand what data went in, what data comes out, how it performs against ground truth. Did you have the diagnosis or not? Was the recommendation used or helpful? With generative AI, "It may be a completely well-developed technology, but based on the prompt you give it, the answer could either be accurate or kill the patient." Halamka offered a real example. "We took a New England Journal of Medicine CPC case and gave it to a commercial narrative AI product. The case said the following: The patient is a 59-year-old with crushing, substantial chest pain, shortness of breath – and left leg radiation. "Now, for the clinicians in the room, you know that left leg radiation is kind of odd. But remember, our generative AI systems are trained to look at language. And, yeah, they've seen that radiation thing on chest pain cases a thousand times. "So ask the following question on ChatGPT or Anthropic or whatever it is you're using: What is the diagnosis? The diagnosis came back: 'This patient is having myocardial infarction. Anticoagulate them immediately.' "But then ask a different question: 'What diagnosis shouldn't I miss?'" To that query, the AI responded: "'Oh, don't miss dissecting aortic aneurysm and, of course, left leg pain,'" said Halamka. "In this case, this was an aortic aneurysm – for which anticoagulation would have instantly killed the patient. "So there you go. If you have a product, depending on the question you ask, it either gives you a wonderful bit of guidance or kills the patient. That is not what I would call a highly reliable product. So you have to be exceedingly careful." At the Mayo Clinic, "we've done a lot of derisking," he said. "We've figured how to de identify data and how to keep it safe, the generation of models, how to build an international coalition of organizations, how to do validation, how to do deployment." Not every health system is as advanced and well-resourced as Mayo, of course. "But my hope is, as all of you are on your AI journey – predictive and generative – that you can take some of the lessons that we've learned, take some of the artifacts freely available from the Coalition for Health AI, and build a virtuous life cycle in your own organization, so that we'll get the benefits of all this AI we need while doing no patient harm," he said.

Full IDE Data Set Demonstrates Statistically Significant Reduction of All-Cause Mortality and Primary Major Adverse Events (MAEs) at 30 days with use of AMDS in Acute DeBakey Type I (ADTI) Dissections Complicated by Malperfusion 72% Reduction in All-Cause Mortality and 52% Reduction in Primary Major MAEs when Compared to Current Standard of Care Hemi-arch Procedure ATLANTA, Jan. 29, 2024 /PRNewswire/ -- Artivion, Inc. (NYSE: AORT), a leading cardiac and vascular surgery company focused on aortic disease, today announced the presentation of results from the AMDS PERSEVERE clinical trial in a Late-Breaking Science presentation at the 60th Annual Meeting of the Society of Thoracic Surgeons in San Antonio, Texas. The data presented analyzed clinical outcomes across the full 93 study participant IDE cohort at 30-days following AMDS implantation. Dr. Wilson Szeto, Chief of Cardiovascular Surgery at Penn Presbyterian Medical Center, presented the data from the PERSEVERE US IDE trial as a late-breaking abstract titled, Results of a Novel Aortic Arch Hybrid Prosthesis for Open Repair of Acute DeBakey Type I Dissection with Malperfusion: 30-day Results from the PERSEVERE Study. Data from the trial demonstrate statistically significant reduction of all-cause mortality and primary major adverse events (MAEs), as well as no occurrence of distal anastomotic new entry (DANE): The data also demonstrate excellent results for secondary endpoints: 1One event remains in adjudication The data compares very favorably with expected rates of early reintervention and DANE tears in this patient population. DANE tears occur in up to 70% of patients following hemiarch repair without AMDS, allowing continued blood flow into the false lumen created by the dissection.2,3 The presence of DANE is associated with enlargement of the aorta, reoperation, and increased mortality. In contrast, DANE has not been detected in any patients in the PERSEVERE study and it was not reported in the DARTS study through 3 years of follow up of AMDS-treated patients.4 Dr. Szeto said, "Acute DeBakey Type I (ADTI) dissections remain one of the most life-threatening emergencies that cardiac surgeons address. Despite the seriousness of the condition, there have been limited surgical advancements in the last several decades, demonstrating an unequivocal need for innovation to better treat these patients. I am extremely encouraged by the results of the PERSEVERE study which indicate that AMDS significantly reduces 30-day MAE's in ADTI patients complicated by malperfusion and helps prevent DANE. The ease of use and approachability of the AMDS device will expand the ability of cardiac surgeons to offer a more comprehensive treatment for these patients amidst a life-threatening emergency." "We are extremely excited to share these overwhelmingly positive results from the PERSEVERE study as they reinforce the unrivaled clinical benefit and life-saving nature of AMDS. Notably, these results show an even greater improvement in all-cause mortality compared to interim data presented in October," said Pat Mackin, Chairman, President, and Chief Executive Officer of Artivion. "We now look forward to quickly completing patient follow up and our PMA submission for AMDS to the FDA and to delivering this revolutionary technology to patients with no comparable alternatives as soon as possible." About the AMDS PERSERVE Clinical Trial The PERSEVERE trial is a prospective, multicenter, non-randomized clinical trial to determine if patients with acute DeBakey Type I aortic dissection can be treated safely and effectively using the AMDS Hybrid Prosthesis. The trial is designed to support the company's forthcoming application to the U.S. Food and Drug Administration (FDA) for premarket approval of the AMDS. The trial consists of 93 participants in the U.S., who have experienced an acute DeBakey Type I aortic dissection. Each participant will be followed for up to 5 years. The combined 30-day safety and primary efficacy endpoints will determine the impact of the AMDS Hybrid Prosthesis on DANE prevention, reducing mortality, new disabling stroke, new onset renal failure requiring dialysis, and myocardial infarction; as well as remodeling of the aorta. About the AMDS Hybrid Prosthesis and DeBakey Type I Aortic Dissections The AMDS is the world's first aortic arch remodeling device for use in the treatment of acute Type I aortic dissections. It is used as a complement to, and in conjunction with, hemiarch replacement without adding technical complexity. The design of the AMDS allows for rapid deployment of the graft in the aortic arch during a standard replacement of the ascending aorta, with deployment adding minimal time to the procedure. The deployment of the AMDS preserves the native arch, allowing for minimally invasive re-interventions if needed, rather than an invasive arch repair. AMDS is available in select markets around the world including Europe, Canada and certain countries in Asia. In the clinical trial (DARTS) supporting the CE Mark and Health Canada approvals, the AMDS was shown to reduce complications and reoperations in comparison to published rates with the standard of care, thereby improving the care of patients and offering potential cost savings for the health care system. Globally, approximately 48,000 patients suffer from acute Stanford Type A aortic dissections annually, an estimated $540 million market opportunity pending regulatory approvals. Aortic dissection occurs when the innermost layer of the aorta tears and blood surges through the tear separating the layers of the aorta. In acute DeBakey Type I aortic dissections, a subset of Type A dissections, the dissection flap originates in the ascending aorta and continues down into the descending thoracic aorta. Left untreated, aortic dissections lead to death in about half of patients within the first 3 days. The current standard of care for repairing acute DeBakey Type I aortic dissections with a primary entry tear in the ascending is a hemiarch repair which involves open chest surgery during which the ascending thoracic aorta is replaced. Though this typically addresses the most critical and pressing issues resulting from acute DeBakey Type I dissections, it is often not enough. Hemiarch repair alone does not address downstream true lumen expansion or treating the false lumen beyond the ascending aorta, which could lead to costly and fatal complications such as malperfusion with subsequent end-organ ischemia resulting from a lack of blood-flow, and continued pulsatile blood flow in the false lumen leading to aneurysmal growth of the aorta. About Artivion, Inc. Headquartered in suburban Atlanta, Georgia, Artivion, Inc. is a medical device company focused on developing simple, elegant solutions that address cardiac and vascular surgeons' most difficult challenges in treating patients with aortic diseases. Artivion's four major groups of products include: aortic stent grafts, surgical sealants, On-X mechanical heart valves, and implantable cardiac and vascular human tissues. Artivion markets and sells products in more than 100 countries worldwide. For additional information about Artivion, visit our website, . References Zindovic I et al. J Thorac Cardiovasc Surg 2019; Pacini D et al. Eur J Cardiothorac Surg 2013; Girdauskas E. et al. J Thorac Cardiovasc Surg 2009; Geirsson A. et al J Thorac Cardiovasc Surg 2007; Bossone E. et al Am J Cardiol 2002 Ravesh M. et al. J Thorac Dis 2021 Bing F et al. Vasc Endovasc Surg 2014, Ergin M, et al Ann Thorac Surg 1994, Rylski B et al. Eur J Cardiothorac Surg, 2017, Tamura K et al, Eur J Cardiothorac Surg 2017 Reference: Bozso et al: The Journal of Thoracic and Cardiovascular Surgery (2022), doi: Company Codes: NYSE:AORT

ATLANTA, Nov. 9, 2023 /PRNewswire/ -- Artivion, Inc. (NYSE: AORT), a leading cardiac and vascular surgery company focused on aortic disease, today announced that it has completed enrollment in the PERSEVERE clinical trial. The PERSEVERE trial is a prospective, multicenter, non-randomized clinical trial to determine if patients with acute DeBakey Type I aortic dissection can be treated safely and effectively using the AMDS Hybrid Prosthesis. The trial is designed to support the company's forthcoming application to the U.S. Food and Drug Administration (FDA) for premarket approval of the AMDS. The trial will consist of 93 participants in the U.S., who have experienced an acute DeBakey Type I aortic dissection. Each participant will be followed for up to 5 years. The combined 30-day safety and primary efficacy endpoints will determine the impact of the AMDS Hybrid Prosthesis on reducing mortality, new disabling stroke, myocardial infarction, and new onset renal failure requiring dialysis, and remodeling of the aorta. Dr. Wilson Szeto, the PERSEVERE National Principal Investigator, Chair of the Steering Committee and Chief of Cardiovascular Surgery at Penn Presbyterian Medical Center, said, "Congratulations to all the investigators and the entire Artivion team for the completion of the PERSEVERE trial. AMDS represents a practice-changing advancement for all cardiothoracic surgeons in the surgical treatment of patients with acute DeBakey type I aortic dissection presenting with malperfusion. Completion of this important trial is an exciting milestone in the field of thoracic aortic surgery. We are hopeful that the study will be positive and demonstrate AMDS as a transformative innovation that will improve the lives of our patients with this devastating clinical scenario." "We are incredibly pleased to have completed enrollment in the PERSEVERE clinical trial. We recently presented overwhelmingly positive interim results of the PERSEVERE trial at the European Association of Cardiothoracic Surgery Meeting in Vienna that demonstrated the lifesaving nature of AMDS, including reduction of stroke, new onset renal failure requiring dialysis and myocardial infraction," said Pat Mackin, Chairman, President, and Chief Executive Officer of Artivion. "The completion of the enrollment of the study keeps us on track to achieve PMA approval in the second half of 2025." About the AMDS Hybrid Prosthesis and DeBakey Type I Aortic Dissections The AMDS is the world's first aortic arch remodeling device for use in the treatment of acute Type I aortic dissections. It is used as a complement to, and in conjunction with, hemiarch replacement without adding technical complexity. The design of the AMDS allows for rapid deployment of the graft in the aortic arch during a standard replacement of the ascending aorta, with deployment adding minimal time to the procedure time. The deployment of the AMDS preserves the native arch, potentially allowing for minimally invasive re-interventions, including the repair of additional entry tears, rather than an invasive arch repair. AMDS is available in select markets around the world including Europe, Canada and certain countries in Asia. In the clinical trial supporting the CE Mark and Health Canada approvals, the AMDS was shown to reduce mortality, complications and reoperations in comparison to published rates with the standard of care, thereby improving the care of patients and offering potentially significant cost savings for the health care system. Globally, approximately 48,000 patients suffer from acute Stanford Type A aortic dissections annually, an estimated $540 million market opportunity pending regulatory approvals. Aortic dissection occurs when the innermost layer of the aorta tears and blood surges through the tear separating the layers of the aorta. In acute DeBakey Type I aortic dissections, a subset of Type A dissections, the dissection flap originates in the ascending aorta and continues down into the descending thoracic aorta. Left untreated, aortic dissections lead to death in about half of patients within the first 3 days. The current standard of care for repairing acute DeBakey Type I aortic dissections with a primary entry tear in the ascending is a hemiarch repair which involves open chest surgery during which the ascending thoracic aorta is replaced. Though this typically addresses the most critical and pressing issues resulting from acute DeBakey Type I dissections, it is often not enough. Hemiarch repair alone does not address downstream true lumen expansion or treating the false lumen beyond the ascending aorta, which could lead to costly and often fatal complications such as continued blood flow in the false lumen, an aneurysmal aorta, and malperfusion with subsequent end-organ ischemia resulting from a lack of blood-flow. About Artivion, Inc. Headquartered in suburban Atlanta, Georgia, Artivion, Inc. is a medical device company focused on developing simple, elegant solutions that address cardiac and vascular surgeons' most difficult challenges in treating patients with aortic diseases. Artivion's four major groups of products include: aortic stent grafts, surgical sealants, On-X mechanical heart valves, and implantable cardiac and vascular human tissues. Artivion markets and sells products in more than 100 countries worldwide. For additional information about Artivion, visit our website, . Contacts: Company Codes: NYSE:AORT