Acute Stroke: A New Target for Endovascular Therapy

Experience and availability make interventional cardiologists uniquely qualified for acute stroke management.

A death due to stroke occurs about once every 4 minutes in the United States, according to estimates from the American Heart Association. Time is of the essence when it comes to effective stroke management. Yet, with a large proportion of U.S. residents living a significant distance from the nearest comprehensive stroke center, the logistics of accessing care within a limited treatment window create a potentially insurmountable obstacle. A patient presenting with acute stroke to a small or rural community hospital, therefore, often receives treatment at a facility that lacks a dedicated neurointerventionalist or requires transport to a dedicated stroke center.

“It is widely known that stroke is undertreated,” Brion M. Winston, MD, an interventional cardiologist at Capital Cardiology Associates in Albany, New York, said in an interview with Cardiology Today’s Intervention. “Too often, I see people who come into the hospital and it seems like they are outside the window for thrombolytic or mechanical intervention, and they are just put to bed. The target becomes harm reduction at that point, but no thought for what you can do upfront.”

At first glance, an obvious solution would be to add neurointerventionalists to hospitals that treat stroke. However, small community hospitals generally lack the case volume needed to provide a full workload for a neurointerventionalist. At community hospitals, the number of stroke cases in these areas fall into a sort of clinical no-man’s land: not enough to justify hiring a dedicated specialist, but just enough to leave a sizable gap in patient care.

“It has been known for 20 years that we are not doing the right job for stroke,” said Christopher J. White, MD, chief of cardiology at Ochsner Heart and Vascular Institute in New Orleans.

However, a momentum shift has been occurring in stroke care, with hospitals increasingly addressing this unmet need by utilizing specialists that Winston said he has heard described as “like bees” in their ubiquity.

“Cardiologists are everywhere — every community has a cardiologist, but not every community has stroke interventionalist,” Winston said. “If I had a stroke, my first choice would be to go to a large academic center with a dedicated, busy neurointerventionalist. But failing that, and failing immediate proximity to a high-volume stroke center, which is something like 90% of this country, I think interventional cardiologists should be the ones to do this.”

In making the case for cardiologist involvement in acute stroke management, data supporting the efficacy of catheter-based stroke treatments certainly add legitimacy to the argument.

“There has been a lot of momentum, just in the last year and especially at the American Heart Association and American Stroke Association’s International Stroke Conference, where, for the first time, vascular stroke intervention started to look pretty good,” White said. “Devices have gotten a lot smaller, easier to use and faster to use. Now, several studies have been published and presented at national meetings. There is a lot of optimism for vascular therapies for stroke.”

A Matter of Time

Given the 3- to 4.5-hour window for initiating IV tissue plasminogen activator (tPA), the need to intervene quickly in cases of acute stroke can be a matter of life or death. However, mortality is by no means the only measure of a poor stroke outcome. According to the American Stroke Association, stroke is a leading cause of disability among adults in the United States. Patients who fail to receive prompt and effective care may be left with incapacitating long-term effects, including paralysis, speech difficulties, confusion, memory loss and other consequences.

“The time from onset of stroke to intervention is absolutely critical,” Mark H. Wholey, MD, director of vascular and neurovascular interventions at the Allegheny Health Network, Pittsburgh, and adjunct professor of engineering in medicine at Carnegie Mellon University, told Cardiology Today’s Intervention. “For every 30-minute delay, there is a 10% increase in problems related to recovery. When you have a stroke, it would be ideal if you could be on the table in 3 hours, but that doesn’t happen very often when patients are being transported long distances. Although less desirable, successful results have been achieved in delays as long as 6 hours, being dependent on the clinical findings and location of stroke.”

Winston, who spent 2 years working at Rapid City Regional Hospital in South Dakota, said he became all too familiar with the challenges facing rural hospitals without stroke specialists on staff.

“This was a busy regional hospital in Western South Dakota, and we were isolated. It was 500 miles to the next cath lab and the nearest neurointerventionalist was in Denver, which was 600 miles away. So, if we had stroke cases, we had to take them for neurosalvage.”

Yet, according to White, who works in a city with two neurointerventionalists handling elective procedures at five hospitals, training the neurointerventionalists to handle stroke in these community hospitals would leave these specialists with a dearth of “daytime jobs.”

“The problem is that the specialty is so narrow there just isn’t enough work for more than one or two [neurointerventionalists] in a city the size of New Orleans,” White said.

However, it is difficult to conceive that two neurointerventionalists could share the full burden of acute stroke management for the entire city of New Orleans, he said. “When you cover stroke, you have to be on call every night. It’s 24/7. When you have two neurointerventionalists in a city this size, there is no way those two can be on call every night. That would make for a pretty miserable life,” he said.

With time working against stroke management — and stroke patients — in many ways, Wholey said the availability of cardiologists could save precious minutes.

“Stroke is one of the last vascular frontiers where a significant number of patients are being excluded because of the lack of trained physicians. Because of their high-volume procedures and skills with devices similar to neurointerventions, cardiologists with adequate training could easily transition into neurointervention,” he said. “The critical element for cardiologists is that they are there, they are available and they are already well trained. You could train an interventional cardiologist to do complex neurointervention in 1 or 2 days, not 1 or 2 years.”

Endovascular Treatment

In the past year alone, a number of large trials examining intra-arterial therapy for the treatment of acute stroke have been presented and published (see Table).

In late December 2014, results of the phase 3, multicenter, open-label MR CLEAN trial were published in The New England Journal of Medicine. Researchers reported that intra-arterial treatment consisting of intra-arterial thrombolysis, mechanical therapy or both plus usual care within 6 hours of stroke onset was safe and effective in patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion of the anterior circulation. This finding was in contrast to results of other randomized controlled trials that did not report a benefit of intra-arterial treatment, the researchers noted in NEJM. Analysis of the primary and secondary outcomes favored the intervention. Rates of serious adverse events during 90 days were similar between the intervention and usual care groups.

At the time of publication, István Szikora, MD, PhD, president of the European Society of Minimally Invasive Neurological Therapy, said in a press release that the MR CLEAN findings may “change the practice of acute stroke treatment in this special group of patients.” However, he added, physicians “must make sure that this delicate technique is being used in proper conditions and delivered by properly trained physicians.”

The positive findings in the MR CLEAN trial were quickly followed by three promising trials presented in February at the International Stroke Conference: ESCAPE, EXTEND-IA and SWIFT PRIME.

In the multicenter EXTEND-IA trial, early endovascular thrombectomy with the Solitaire FR stent retriever (Covidien) was associated with improved outcomes compared with alteplase only in 100 randomized patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue.

In the multicenter ESCAPE trial of 316 imaging-selected patients with acute ischemic stroke who had a proximal vessel occlusion, a small infarct core and moderate-to-good collateral circulation, rapid endovascular thrombectomy was associated with reduced mortality and improved functional outcomes.

In the multicenter SWIFT PRIME trial, IV tPA plus endovascular thrombectomy with the Solitaire FR or Solitaire 2 stent retrievers was associated with less stroke-related disability compared with IV tPA alone in the cohort of 196 patients with acute ischemic stroke due to large vessel occlusion.

All three trials were stopped early due to efficacy.

The stent retrievers studied in MR CLEAN and the others consist of a “stent which is deployed via angiogram within the thrombus that is blocking the artery in the brain and then withdrawn under negative pressure suction with the aim of retrieving the thrombus,” Bruce C.V. Campbell, MD, from the department of neurology at Royal Melbourne Hospital in Victoria, Australia, and investigator for the EXTEND-IA trial. He told Cardiology Today’s Intervention that he anticipates that the results of the recent trials “will truly revolutionize the way we treat large vessel occlusion stroke and transform the outcomes for this most severely affected group of patients.”

“All of these trials now have shown that there is a definite beneficial advantage, in terms of patients being able to function without major disability with a combination of IV tPA and then a transfer for interventional therapy with one of the retrieval devices,” Wholey said.

Unique Qualifications

In many ways, interventional cardiologists are uniquely suited to management of vascular procedures of all kinds, Wholey told Cardiology Today’s Intervention.

“Cardiologists are almost naturally trained and skilled for all vascular compartments, whether it is the peripheral circulation, where they have been very strong over the past 7 or 8 years, or the coronary circulation,” he said. “Their basic training is such that they spend their careers handling the 0.014-in wires and the guiding catheters and the vascular management of the patient. I think the transition to the carotid circulation, both extracranial and intracranial, is not a difficult course.”

White said cardiologists who perform carotid stenting already are familiar with the vessels of the neck. “The most important competency is what we call cervical competency, which is the ability to access the vessels in the neck. We learn that when we do carotid stenting. You use the same catheters in carotid stenting that you would use for endovascular intervention for stroke,” he said.

He further noted that approximately 70% of physicians who perform carotid stenting are cardiologists, making them an intuitive choice to be part of a multidisciplinary stroke team.

Winston, who is fellowship trained and board certified in endovascular interventions, also does noncoronary procedures, including carotid stenting. Although some cardiologists would need additional training in neuroanatomy, many aspects of stroke management are already second nature to cardiologists, he said.

“From a technical standpoint, we are accustomed to working very quickly, working in small vessels and, of course, working with a beating heart, which is challenging compared to other vascular beds,” Winston said. “Also, we work with a team and we interface with the emergency departments and emergency medical services. There is a scaffold, if you will, for other emergency systems of care, such as acute stroke intervention.”

In the May issue of Catheterization and Cardiovascular Interventions, Nay Htyte, MD, MS, and colleagues published data showing that interventional cardiologists who participated on a stroke management team achieved comparable outcomes to neurointerventionalists when performing catheter-based stroke interventions. The study evaluated outcomes of 124 patients with acute ischemic stroke who received catheter-based therapy at Ochsner Medical Center from 2006 to 2012. At 90 days, the findings revealed no significant differences in patient outcomes for those treated by an interventional cardiologist or a neurointerventionalist.

L. Nelson Hopkins, MD, FACS, distinguished professor of neurosurgery at the State University of New York at Buffalo, said “the cardiologist, as a team member, could be extraordinarily powerful at treating stroke.” But he noted that there may be some resistance to embracing the role of cardiologists in acute stroke management due to “turf politics.” However, he acknowledged that “there is no such thing as a situation [in medicine] where there aren’t turf issues.”

For White, the aforementioned study “puts that issue to bed.”

A National Quality Mandate

According to White, the inability to reconcile the dilemma of proximity, availability, time and professional boundaries has led to “an unacceptable scenario” in terms of patient care delivery.

“We have had the door-to-balloon time for MI for 10 years and it has been a national quality mandate; CMS publicly reports it,” he said, questioning why the same does not exist for a door-to-balloon time for stroke.

White said he believes there is a need for the establishment and implementation of national standards for stroke at all hospitals. “There are, in this country, comprehensive stroke centers that don’t have enough neurointerventionalists to actually staff the hospitals 24/7. The mandate should be that the comprehensive stroke centers should all be able to deliver door-to-balloon time of 90 minutes, just like with heart attacks,” he said.

Introducing a uniform standard would shift the focus from professional competition back to hospital accountability and patient care, White said.

Multidisciplinary Team

The skills of trained cardiologists for acute stroke management would best be deployed within the context of a multidisciplinary team of neurosurgeons, neurologists, radiologists and cardiologists, according to Hopkins.

“It might be different at each institution, but those are the major specialties that would potentially be involved in the interventional treatment of stroke,” he said.

“I think we can get things moving if we stop debating who is better at this or that. What will make it work will be who’s there. We call it a ‘coalition of the willing.’ Who wants to help with this? Then make your team and say, ‘OK, here’s how we are going to do it,’” White said.

He noted that Ochsner put together a team that works well together and provides all of the skills needed to handle treatment of acute stroke. “You have to meet all of the needs with your team. So, if the cardiologist is on call, we have to have a neurologist paired with him. When the neuroradiologist is on call, we don’t need the neurologist because he can do that work. It is all about balance, and I think we have been able to do that very well,” White said.

Wholey, a board-certified interventional radiologist, told Cardiology Today’s Intervention that the “interventional radiologists are willing participants in the search to expand treatment for stroke.”

Winston cautioned that not all cardiologists should be automatically considered qualified to handle stroke management; additional training and requisite equipment may be needed. “You have to be able to interpret a CT scan or an MRI of the brain for the major findings, such as acute intracranial hemorrhage. For that, a cardiologist needs dedicated experience, dedicated training, fellowship training,” he said. Winston recommended courses such as the CLOTS Training Course for Acute Stroke Management, a comprehensive, 5-day training course offered by the Society of Interventional Radiology. The course provides training in stroke pathophysiology, clinical neurological evaluation, multimodal imaging and catheter-directed stroke management, with a focus on multidisciplinary collaboration.

Moreover, multidisciplinary collaboration is becoming more and more possible every day, with the advent of telemedicine and medical apps, Wholey said.

“All of these procedures are going to become virtual very soon” he said. “In other words, the iPhone is going to become medicalized. You’re going to have information on your iPhone transferred almost immediately to a referral center. So as this technology advances, this virtual transfer of information is going to allow the community hospital to obtain expert opinions. The information is going to be shared from hospital to hospital and patient to doctor a lot more efficiently now than it has been in the past.”

Hopkins said a cardiologist managing stroke at a community hospital could collaborate remotely with specialists at stroke centers.

“A cardiology center in a smaller town can communicate with a neurocenter in a large city and make an intelligent decision,” he said. “Once that decision has been made, the actual procedure to open up the artery is something cardiologists do all day, every day.”

According to Wholey, the multidisciplinary stroke team is, without doubt, the way of the future.

“The multidisciplinary team is everything,” he said. “I see putting together a leadership group to organize cardiology and establish training periods, a 1- or 2-day training period in Minneapolis and in San Diego and in San Francisco, so that cardiologists get educated. I think it is an easy transition, and a critical transition for cardiology.” – by Jennifer Byrne

• References:
• Berkhemer OA, et al. N Engl J Med. 2014;doi:10.1056/NEJMoa1411587
• Campbell BCV, et al. N Engl J. Med. 2015;doi:10.1056/NEJMoa1414792.
• Goyal M, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1414905.
• Htyte N, et al. Catheter Cardiovasc Interv. 2015;doi:10.1002/ccd.25755.
• Jovin TG, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1503780.
• Saver JL, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1415061.

• For more information:
• L. Nelson Hopkins, MD, FACS, can be reached at 875 Ellicott St., Buffalo, NY 14203; email: lnhopkins@icloud.com.
• Christopher J. White, MD, can be reached at 1514 Jefferson Highway, New Orleans, LA 70121; email: cwhite@ochsner.org.
• Mark H. Wholey, MD, can be reached at 320 E. North Ave. CVI I – NW Wing, Pittsburgh, PA 15212; email: markwholey@aol.com.
• Brion M. Winston, MD, can be reached at 7 Southwoods Blvd., Albany, NY 12211; email: brion.winston@gmail.com

Disclosures: Hopkins, White, Wholey and Winston report no relevant financial disclosures.