The future of aortic disease: Our ‘aneurysm moonshot’

Over the last 25 years, the course and pace of change in the treatment of aortic disease has been great. Endovascular intervention has forced us to interact with the aortic wall instead of just resecting it. In turn, this has taught us so many new truths about the pathophysiology of aortic disease that a well-studied surgeon from three decades ago would be unfamiliar with most controversies that exist today: modes of endograft failure, treatment of endoleaks, durability of branched repair, and imaging advances for intraoperative augmented reality, to name a few. In this time, vascular surgeons have become Interventionalists, scalpels have been replaced with ionizing radiation, and the field of vascular medicine has been pioneered. As we stumble quickly toward the holy grail of Total Endovascular Aortic Repair with new advances in arch device technology and an evolving understanding of the way this disease plays out on the molecular stage, it is notable that 2016, and this focused aortic issue of Vascular Medicine, coincides with the 25th anniversary of Dr Parodi’s publication of the first description of endovascular aneurysm repair (EVAR). ¹ It is with this august event in mind that it is timely to pause to reflect on its impact on the course of vascular history, as well as to attempt an educated conjecture of where the next 25 years might lead.

Although historians could regale us with a variety of novel attempts at intervention over hundreds of years in the past, conventional open aortic surgery in its modern form has been around in earnest since 1950. Over the course of its maturation, surgeons were able to refine both the indications for intervention and techniques to improve outcomes. Most would agree that the arc of innovation has plateaued for open aortic surgery, and renowned groups who pioneered conventional surgery are now publishing data reflecting outcomes from the ‘modern era’ that span over 30 years ² and showing time-tested outcomes for this robust technique, but also revealing its unforgiving nature in the old and infirm. Indeed, open thoracoabdominal surgery is not for the frail, and is in desperate need of a minimally invasive solution. The cautious observer might reflect that the evolution of endovascular surgery is following the same iterative course as open surgery, with early adopters experiencing early failures leading to the evolution of more robust and durable treatments in real time. However, the pace of change is so rapid that it is challenging to know where we are in the evolutionary arc as it unfolds. Many, including myself, hold hope that there are still generations of endovascular devices to come that will perfect the technique before the innovation plateaus, but history will be the final judge.

The endovascular era has forced surgeons to work with the aortic wall as part of the repair. What this has meant is rather than resecting disease, we have been able to observe its response to treatment. This has had two interesting consequences. The first is in the situation when endovascular repair fails. Device failure provides insight into the natural progression of the disease, and has informed our current understanding that aneurysm disease is a systemic disease of the entire aorta which manifests in adjacent territories chronically over time. Weighing this against the projected lifespan of the patient has provided insight into the surveillance needed to prevent subsequent aortic-related mortality. As with most fields, the failures we have witnessed have been almost more valuable than the successes in helping to innovate the approach to treatment.

The second is in the situation when endovascular repair succeeds and the aneurysm sac regresses without pressurization, lending credence to the importance that circulatory pressure and ongoing systemic stress has on the progression of disease.

Reflecting on this focused issue of Vascular Medicine and the future of the field of aortic disease, it is easy to be overwhelmed with the breadth and scope of the expansion of our field. In these few paragraphs, it would be impossible to predict the timeline and scope of change if the current rate of acceleration is maintained in what feels like all directions. The advent of isovoxel imaging three decades ago brought with it the ability to manipulate the aorta in three dimensions (3D) before cutting skin – and provided an invaluable tool for planning surgery that eventually obviated the need for a large incision at all. This one innovation ushered in the era of complex endovascular repair. These 3D images are now used in operating rooms throughout the modern world to create an augmented reality – and fusion imaging techniques have started a trend to decrease the need for ionizing radiation in endovascular procedures. As we start to apply navigation techniques from other fields to the practice of aortic surgery, the tracking modality that will be used to replace radiation could be any number of technologies including electromagnetic guidance, some variant of global satellite positioning or some other as yet unimagined force. Devices, now being made of stainless steel or nitinol, and polyester or ePTFE, often with an element of manual labour, may someday be printed with 3D printers and biomaterials, thus shortening the manufacturing delay and improving customization, durability and biologic interaction. Delivery systems, which have been continually decreasing in profile, will become even smaller, until eventually tissue-specific cell targeting may limit the need for mechanical intervention in aortic disease in all but the most advanced conditions.

Although it is easy to be excited about the technological advancements we are seeing arise daily, it is more exciting to imagine that they are only a temporary stop on the path to medical prevention of aneurysm disease. Thus, the area of this field I feel is most pertinent to the readership of this Journal, and likely the uncharted path for the far future, lies not in mechanical solutions to aortic disease, but rather at the interface between surgical and medical realms. The thin red line that divides surgeons and medical specialists is shifting as our understanding of the disease becomes more mature. Much like the treatment of Helicobacter pylori has virtually extinguished the use of vagotomy and distal gastrectomy for the treatment of gastric ulcer, ‘best medical management’ for cardiovascular disease is beginning to change the indications for intervention in coronary artery disease, and will likely do the same for aneurysms and dissection.

The first step in this path is fully fleshing out the phenotypes for the individual patients for whom we are caring. Until now, the presence or absence of many additional comorbidities in patients with aneurysms have been regarded as coincidental, or perhaps part of a ‘metabolic syndrome’. The articles by Gray et al., ³ Takagi and Umemoto, ⁴ Batagini et al., ⁵ and Nader et al. ⁶ in this issue of Vascular Medicine show the work being done to understand the comorbidities accompanying aortic disease and the impact they may have on our current success with intervention. Once these patterns of comorbidities are better understood, it will then be incumbent on us to find the molecular basis by which these clusters of conditions occur, and use this knowledge to engineer new biologic tools. This narrative is being written daily as the individual genes culpable for different clinical presentations of aortic disease are being discovered en masse. ⁷ It is becoming a tangible reality that, as we unravel the cause for the vessel wall deterioration that leads to aneurysmal degeneration, we will discover a way to reverse or prevent it.

It will be a challenge to ensure that the progress we are making can be shared globally in a field that is already divided by jurisdictional resources. In modern times, despite the proven benefit of endovascular repair for the treatment of aneurysms, and the advanced imaging required to provide it, patients who develop an aneurysm in many parts of the world do not have access to this technology. And, although it could be argued that cardiovascular disease is a luxury known only to well-resourced populations, discovering its genetic basis will provide an ethical imperative to make biologic interventions available globally. The need for cardiovascular prevention will grow as the sedentary western lifestyle becomes more widespread, and a renaissance of cardiovascular disease occurs in developing nations. As it is only recently that some developed countries have included mandatory screening for abdominal aortic aneurysm for men aged 65 (an intervention that is simple and proven effective in reducing aneurysm-related mortality), the thought of global initiatives for widespread use of novel biologic tools for aneurysm prevention seems very far away, and a place we will only reach if we are all dedicated to getting there. The challenge for the future thus will be not only to determine the methods for preventing aneurysm disease, but to find a way to extend the advances in medical treatment to anyone in need.

After careful reflection, and pondering the manuscripts assembled for this issue of Vascular Medicine, it is clear that the future for the treatment of aortic disease is bright. The pace of innovation has been swift, and the current leaders have not been afraid to challenge the dogma to redefine the field and find better ways to treat this disease. Now that we have proven that disruptive ideas are welcome, and effective, in this field, an ‘aneurysm moonshot’ seems well within our reach. I’d say the best prediction anyone can make about the future of treatment of aortic disease is that the next 25 years will most definitely be as exciting as the last.