Driving Clinical Transformation for the Acute Stroke Population

 

Stroke is a global disease, one that is increasing as people age and life expectancies increase. In the United States, stroke is the leading cause of disability and the fourth-leading cause of death.

Pharmacological intervention, increasingly sophisticated surgical techniques and ever-advancing imaging technologies, however, offer hope that these sobering facts can be changed.

Collaboration among clinical specialties, laboratory researchers, and industry vendors is the key to realizing that hope. Perhaps no one knows that more than does Adnan H. Siddiqui, MD. Dr. Siddiqui is Professor and Vice Chairman of Neurosurgery at the University at Buffalo School of Medicine, Director of the Toshiba Stroke and Vascular Research Center (TSVRC), Director of Training and Education at the Jacobs Institute (JI), and the Director of Stroke Service at the Gates Vascular Institute (GVI), all located in Buffalo, NY.

“The GVI operates on the principle of multi-specialty collaboration. Upon admission, every stroke patient is evaluated by specialists that include neurologists, neurosurgeons, cardiologists, and other medical specialists working together as a team,” said Dr. Siddiqui. “GVI houses two of the world’s most advanced Toshiba 320-slice CT scanners, which facilitate decision making by their ability to produce an entire brain perfusion scan, a temporally resolved (4D) map of the entire blood vasculature (arteries and veins) from the chest to the top of the head, and a plain brain scan, all within 5 minutes. This enables the team to make decisions rapidly with respect to treatment options, whether to open surgical intervention, an endovascular procedure, or medical therapy.

“Every relevant clinical discipline works together rapidly to develop the best treatment for each patient,” Dr. Siddiqui added. “We firmly believe that this improves outcomes for stroke patients, many times enabling some of them to fully recover.”

Dr. Siddiqui will be presenting during an evening event at this year’s RSNA meeting in Chicago on how GVI, JI, and the TSVRC are driving clinical transformation for the acute stroke population.

The GVI is located in a $291 million facility adjacent to Buffalo General Medical Center, which it shares with the University at Buffalo (UB) Clinical and Translational Research Center (CTRC). With clinical facilities on the lower floors and research labs on the upper ones, the building is designed to foster collaboration between scientists and clinicians. The architectural design of GVI consists of endovascular catheterization labs and surgical operating rooms ringing a central communal area where clinicians of all vascular specialties co-mingle. This center is the result of the vision of neurovascular surgery pioneer Dr. L. Nelson Hopkins to develop a center based on his many decades of experience running the annual Jackson Hole Vascular Conferences, where specialists from all vascular specialties discussed the toughest cases with each other, with academic researchers, and with research and development engineers from all the major and minor companies in attendance. The dialogue that took place and the cross-pollination of ideas, which resulted in new and novel strategies, convinced him that having this interaction daily would be nirvana for a global vascular center.

He therefore desired to establish a center in Buffalo, with its epidemic of cardiovascular and cerebrovascular disease—50% higher than anywhere else in New York State and as high as the areas within the Southeastern U.S. Stroke Belt. He hoped the center would lead to all the different vascular disciplines working together to speed up the process of advancing vascular medicine and intervention, facilitate the process of research, and incorporate entrepreneurship with both federal and state resources and industry support.

The task of putting these myriad groups in one structure under one vision resulted in the genesis of the Jacobs Institute. The JI serves as the partnership manager, what Dr. Siddiqui equates as a “functional Switzerland” between all the different constituencies at GVI and CTRC. It is an independent, non-profit institute created in partnership with UB and GVI as well as support from private philanthropists. It is a freestanding facility that is connected to a hospital, governed and led by a team of multidisciplinary physicians focused on minimally invasive treatment and prevention of vascular disease. The institute is a global magnet for training of physicians, engineers and executives in the latest vascular technologies using simulators and flow models, as well as coordinating live-case demonstrations at GVI and facilitating new device testing and novel development initiatives.

The Toshiba Stroke and Vascular Research Center, meanwhile, incorporates neuroradiology, neurology, neurosurgery, radiation physics, biomedical and aerospace engineering, and polymer chemistry. Researchers there are focused on image optimization and dose reduction, device development, and hemodynamics to better understand the pathological mechanisms that produce brain aneurysms and cause stroke.

Dr. Siddiqui explained that the center is unique in that it concentrates on the interventional aspects of stroke, in addition to the more common aspects of basic science investigation. The center has developed facilities and capabilities to rapidly evaluate emerging technologies in both the visualization of devices and their effectiveness in intervention. Research performed over the past decade has resulted in medical devices that have had a significant impact on treatment for both ischemic and hemorrhagic stroke and subsequently improved outcomes in patients suffering from major, previously disabling or fatal strokes.

Dr. Siddiqui and his colleagues have been focused on two major aspects of intervention in the research lab and several more in the clinic.

“We are developing better visualization for the tools we use to treat stroke, both hemorrhagic and ischemic,” Dr. Siddiqui said. “Truly phenomenal imaging technology is enabling us to visualize the tools in exquisite detail, not possible with current X-ray technology without significantly increasing the X-ray dose. A specialized camera works similar to the microscope we use during open brain surgery. Micro-angio fluoroscopy shows us how tools are interacting with the vessels and the disease process, which leads to safer and more effective utilization of the currently available technology.”

They have been working with start-up and established companies to utilize both next-generation interative and disruptive technologies to evaluate revascularization efficiencies, both in flow models and animal models of ischemic stroke. They are also participating in a large number of U.S. Food and Drug Administration (FDA)-regulated clinical trials that evaluate technologies to continuously improve interventional treatments for cerebrovascular disease. Aspects of pharmacologic manipulation that may have a neuroprotective effect when dealing with both hemorrhagic and ischemic strokes are being investigated. These include varied strategies such as hypothermia and pharmacologic manipulation with agents that may reduce secondary injury from neuroinflammation that occurs after a stroke.

Dr. Siddiqui is a principal investigator in three major device trials. These include the 3D separator trial, which evaluates stent retriever utilization compared to aspiration with a separator device. The SWIFT PRIME trial is evaluating patients who experience an acute ischemic stroke due to large-vessel occlusion. Stroke patients are randomized to receive either an intravenous recombinant human tissue plasminogen activator (IV t-PA) drug only, or to receive IV t-PA along with mechanical revascularization with the Solitaire stentreiver device.

The POSITIVE randomized clinical trial, which began enrolling patients in mid-2014, is aimed at determining the safety and efficacy of intra-arterial reperfusion in acute ischemic stroke patients who cannot receive IV t-PA because of contraindications or because they present too late for t-PA to work effectively. Advanced perfusion imaging is used to identify patients who are most likely to benefit from revascularization. The purpose of the trial is to demonstrate the safety and efficacy of mechanical thrombectomy over current practices of medical therapy used to treat acute ischemic stroke patients. The trial plans to enroll up to 600 patients at up to 35 participating hospitals in the U.S.

“We are hopeful that the outcomes of these trials, along with dozens of other stroke-related clinical trials being conducted throughout the world, will show how new technologies can change the outcome for patients and offer hope to stroke victims,” said Dr. Siddiqui.

“We want to change the way that stroke is perceived and treated. The mindset that currently exists in the United States and Europe is that a heart attack or myocardial infarction is a very treatable condition but acute ischemic stroke means either permanent disability or death. When the first signs of a stroke are seen, patients need to be rapidly brought to hospitals where they can receive the interventions that may enable them to return to a premorbid quality of life status. Although older people are more likely to have a stroke, they may potentially have many years of life that should have a good quality and be more than endurance of disability. Similarly, for younger patients, a return to premorbid status means preservation of their economic and physical viability and maintained benefit to society.”

Dr. Siddiqui acknowledged that this could be a Herculean task. He said that in the United States, only 2% to 3% of patients eligible for intravenous thrombolytic therapy actually receive the treatment. And the number of patients who get intervention is only a tiny fraction of the first number.

“There is so much room for improvement and tremendous value to change the stroke narrative. I am really excited about the innovative work I am involved with at GVI, and am happy to participate in the cutting-edge research bringing new clinical trials and options for treatment,” he said. “I hope very much that the work and research we are doing in Buffalo will benefit a very large number of patients the world over.”