A distinctive multistakeholder partnership spearheaded by Cleveland Clinic is aiming to improve the odds for patients with acute aortic dissection and other diseases of the thoracic aorta.
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The Multidisciplinary Study of Ascending Tissue Characteristics and Hemodynamics for the Development of Novel Aortic Stentgrafts (MATADORS) brings together Cleveland Clinic surgeons and biomedical engineers with R&D leaders from the top five endovascular stent graft medical device companies and with U.S. Food and Drug Administration staff.
The project, which began in 2016, has two goals:
- To closely study and better understand the tissue architecture and molecular changes involved in the pathogenesis of aortic dissection and aneurysms
- To develop optimal criteria for testing new endovascular devices to treat the ascending aorta, as no such devices are currently approved by the FDA
Focusing multiple experts on the same solution
“MATADORS is a study that has brought together many of us from different disciplines with the understanding that we have a host of unanswered questions about aortic disease, which is a growing epidemic of often fatal problems,” says Eric Roselli, MD, Surgical Director of Cleveland Clinic’s Aorta Center.
The partnership is orchestrated by Kelly Emerton, PhD, Senior Director of Product Development and Commercialization at Cleveland Clinic Innovations, the commercialization arm of Cleveland Clinic. She explains the project’s genesis as follows: “In the past, when I would meet with clinicians to move their ideas forward, I would note that we have prototyping capabilities for R&D and we have researchers in biomedical engineering. The thought was that we could cohesively work across various Cleveland Clinic institutes to drive a project forward, given our internal expertise, and then marry that with FDA and industry, thereby bringing all parties to the table. The concept behind MATADORS was to orchestrate an unprecedented alliance to better design endovascular treatments and develop better verification and validation testing parameters for devices used to treat ascending aortic diseases.”
Acute aortic dissection poses unmet needs
Indeed, there is a great unmet need for new approaches to thoracic aortic diseases, which are estimated to kill more than 40,000 people in the U.S. annually. The incidence appears to be rising, although this may be due in part to increased detection via wider use of chest CT scans.
About 5,000 open surgical repairs are performed annually in the U.S. for acute aortic dissection specifically, but that’s thought to represent only about half of the total need. It’s unknown how many people die at home with the condition undiagnosed, but data suggest acute aortic dissection may account for 8 to 10 percent of sudden deaths, Dr. Roselli says.
Even when patients do reach the hospital, many are deemed unsuitable for open corrective surgery, which involves putting the patient on cardiopulmonary bypass, excising the damaged tissue and replacing it with a graft.
Cleveland Clinic’s outcomes in acute aortic dissection are superior to U.S. and world averages, with a mortality rate of about 5 to 10 percent following emergency surgery compared with nearly 20 percent elsewhere. And at Cleveland Clinic, only about 7 to 8 percent of candidates are deemed unfit for the open procedure, typically for reasons such as coma, cardiac arrest, extreme comorbidities or extensive gut gangrene.
“But we can still do better,” Dr. Roselli notes. “We don’t operate on all patients. The disease process, combined with the need for a major emergency operation, is a serious problem. In elective situations, surgical mortality is less than 1 percent. If we had a less invasive way to treat dissection in dire situations, we could perhaps bridge patients during the acute emergency and then do an elective operation later.”
Dr. Roselli and the Aorta Center team have published heavily in this area, and Cleveland Clinic’s Department of Thoracic and Cardiovascular Surgery is deeply vested in accruing clinical data for better care of patients with dissection.
Study is underway, with first data due soon
MATADORS has already enrolled more than 60 of a planned 400 patients who fall into one of the following arms:
- Patients with ascending dissection (study population)
- Patients with ascending aneurysm (disease control group)
- Transplant recipients or patients needing root replacement without aneurysm (non-disease control group)
Ultrasound images are taken intraoperatively while the chest is open, to directly examine in situ biomechanical properties of the ascending aorta. Resected specimens are analyzed in detail for biomechanical, histologic and hemodynamic properties. Genetic information is also being analyzed.
Snapshots of a few of the study methods employed in MATADORS. Top left: Computational modeling of simulated flow and compliance of the ascending aorta. Top right: Uniaxial testing of extracted specimens to compare in vivo and ex vivo mechanical properties of ascending aortic tissue in acute dissection versus nondissected tissue. Bottom left: Analysis of resected samples from aortic dissection and aneurysm patients to evaluate histopathology and biomechanical properties of ascending aorta regions. Bottom right: Histopathologic evaluation of dissected tissue to assess proteoglycan/glycosaminoglycan content and ratio within treatment groups and within regions of the aorta.
Such information will be essential for device development. “If we are putting in devices without cutting tissue out, we need to really understand how the stent will interact with the tissue, including how strong it needs to be,” Dr. Roselli explains.
The project is exploiting what’s likely to be a short time window, he points out: “We’re moving more and more to endovascular approaches for treating various segments of the aorta, but we’re still doing open surgery on the ascending aorta. So as long as we’re cutting out pieces of tissue, we might as well study them from as many perspectives as possible.”
The team has a manuscript submitted regarding two novel proteins discovered in the aortic wall among the first 60 MATADORS patients. That will be followed by another on results from biomechanical testing showing varied behavior of tissues in different aorta segments, as well as a manuscript on the team’s in vivo epiaortic imaging findings.
“We’re just starting to scratch the surface,” Dr. Roselli says. “I think we’ll see an abundance of other really important research as this effort grows.”
New model for device development?
Dr. Emerton notes that the industry leaders have joined the collaboration to identify commonly adopted end points for their device development while still guarding their respective proprietary information. “All the participants will design their devices independently,” she explains, “but they’ll uniformly use these data to drive better design inputs and to determine, in conjunction with the FDA, the best methods for testing safety and efficacy.”
She describes the initiative as a new model to be applied to any number of clinical challenges: “We plan to get the key parties together at the table to design better regulatory testing to evaluate these devices and get them out the door faster, more efficiently and better designed to help patients.”