Conflict of interest: Nothing to report.
Peripheral Vascular Disease
Acute stroke intervention by interventional cardiologists†
Article first published online: 16 DEC 2008
Copyright © 2008 Wiley-Liss, Inc.
Catheterization and Cardiovascular Interventions
Volume 73, Issue 5, pages 692–698, 1 April 2009
How to Cite
DeVries, J. T., White, C. J., Collins, T. J., Jenkins, J. S., Reilly, J. P., Grise, M. A., McMullan, P. W., Badawi, R. A. and Ramee, S. R. (2009), Acute stroke intervention by interventional cardiologists. Cathet. Cardiovasc. Intervent., 73: 692–698. doi: 10.1002/ccd.21927
- Issue published online: 23 MAR 2009
- Article first published online: 16 DEC 2008
- Accepted manuscript online: 16 DEC 2008 12:00AM EST
- Manuscript Accepted: 29 NOV 2008
- Manuscript Received: 18 NOV 2008
- peripheral vascular disease;
To report the technical success and clinical outcomes of catheter-based therapy (CBT) for acute ischemic stroke in patients ineligible for intravenous thrombolysis.
Acute ischemic stroke is common but undertreated. CBT for acute ischemic stroke is a therapeutic option in selected patients who are not candidates for intravenous thrombolysis.
Consecutive stroke patients who were ineligible for intravenous thrombolysis and underwent CBT were identified by retrospective chart review. Demographic information, National Institutes of Health Stroke Scale (NIHSS), procedural characteristics, and clinical outcomes during hospitalization and at 90 days follow up were collected. Experienced interventional cardiologists with the consultative support of stroke neurologists were on call for acute strokes.
A total of 33 acute ischemic stroke patients underwent emergency cerebral angiography, with 26 patients undergoing CBT. Successful “culprit” artery recanalization was achieved in 23 (88%) of the 26 patients. In-hospital adverse events occurred in 4 (15%) patients, with intracerebral hemorrhage (ICH) (12%) representing the most common adverse event. The baseline NIHSS for patients who underwent intervention was 16.5 ± 9.9 (median 16) and improved significantly to 9.9 ± 8.7 (median 9) (P < 0.001) at hospital discharge. A modified Rankin score of two or less (indicating mild disability) was achieved in half (n = 13) of the CBT treated patients. All cause mortality at 90 days was 8% (2/26).
In selected patients, CBT provided by qualified interventional cardiologists supported by stroke neurologists, offers a safe and effective option for patients with acute stroke who are not eligible for intravenous thrombolysis. © 2008 Wiley-Liss, Inc.
Stroke affects 700,000 patients yearly in the United States and is projected to rise to one million by the year 2025 . Nearly 90% of these strokes are ischemic and 70–80% of ischemic strokes are attributed to large cerebral vessel occlusion [2, 3]. Strokes are the third leading cause of death in the United States and are the most common cause of adult disability, costing more than 65 billion dollars in hospitalization and lost productivity in 2008 .
Prior to the mid 1990's, there was little to offer stroke patients other than supportive care. In 1995, intravenous thrombolysis became the first approved reperfusion therapy for acute ischemic stroke, based largely upon the modest benefits demonstrated in the National Institutes of Neurologic Disorders and Stroke (NINDS) stroke study . More than a decade after the approval of intravenous thrombolytic therapy by the Food and Drug Administration (FDA), the impact on stroke outcome remains muted. It is estimated that only 2–5% of all patients presenting with ischemic stroke receive intravenous thrombolysis. The primary reason for exclusion is the narrow time window (<3 hr) from the onset of symptoms to treatment [5–8]. Though efforts are underway to educate the public about the warning signs of stroke and the need to seek care rapidly, the estimated ceiling of eligible patients who could benefit from intravenous thrombolysis remains ∼1 in 5 of all ischemic stroke patients . This has prompted interest in alternative reperfusion strategies to overcome barriers to treatment with systemic thrombolytic therapy. Catheter-based therapy (CBT) for acute stroke, like direct angioplasty for acute myocardial infarction, has emerged as an attractive reperfusion strategy offering a variety of options including intra-arterial thrombolysis, mechanical thrombectomy, and/or angioplasty with bailout stent delivery (Figs. 1 and 2).
Intra-arterial thrombolysis improves outcomes for selected patients with middle cerebral artery (MCA) occlusion up to 6 hr after the onset of stroke . Despite a Class I recommendation from the American Heart Association/American Stroke Association joint guidelines, CBT with intra-arterial lysis is not an FDA-approved therapy [11, 12]. The mechanical embolus removal in cerebral ischemia (MERCI) trial led to the FDA approval of the Merci Retrieval System (Concentric Medical, Mountain View, CA) for mechanical thrombectomy of large cerebral vessels . Since its initial approval, this device has been redesigned, resulting in improved recanalization rates, especially when used in conjunction with other modalities . The penumbra device (Penumbra, San Leandro, CA) is an FDA-approved thrombectomy catheter, which demonstrated promising results in a recently reported efficacy trial . Yet, despite the potential benefits of CBT for acute ischemic stroke in patients not eligible for intravenous thrombolysis, the limited workforce of interventional neurovascular specialists (385 nationwide) limits access to around-the-clock CBT for stroke patients .
With this in mind, we report the safety and clinical efficacy of CBT for acute ischemic stroke patients not eligible for intravenous thrombolysis performed by interventional cardiologists. We used the existing infrastructure of the cardiac catheterization laboratory including 24/7 on-call catheterization laboratory staff, and the interventional skills of experienced cardiologists with carotid stent experience to provide CBT with consultative support from stroke neurologists.
Institutional review board approval was obtained to conduct a retrospective chart review identifying consecutive ischemic stroke patients ineligible for thrombolysis who received emergent angiography and/or CBT between September 2002 and July 2007. All patients or their legal representatives gave informed consent for their procedure. The stroke neurologist in consultation with the interventional cardiologist on-call determined the patient's suitability for CBT. Each of the interventional cardiologists had performed >50 carotid stent procedures. Eligible patients were ≤8 hr from symptom onset and had no evidence of intracerebral hemorrhage by computed tomography scanning. All patients had neurologic assessment with the National Institute of Health Stroke Scale (NIHSS)  performed by a neurologist at presentation and prior to discharge. No specific cut-off or lower limit for NIHSS was used to exclude patients from CBT; rather, patients were eligible for CBT if they had a serious deficit, even if the corresponding NIHSS was comparatively low (e.g. monocular blindness).
In patients who underwent CBT, unfractionated heparin was given to achieve an activated clotting time of ≥250 sec. The decision to treat with CBT was at the discretion of the operator. Options available included intra-arterial thrombolysis, balloon angioplasty, stent placement, guidewire disruption of thrombus, mechanical embolectomy, or combinations of these modalities. Demographic information, procedural characteristics, NIHSS, and in-hospital outcomes were collected from chart review. Vital status at 90 days was assessed using the Social Security Death Index . Modified Rankin  scores were calculated based on documented exams at 90 days after the procedure.
Our primary endpoint was the proportion of patients with slight or no neurologic disability at 90 days, as defined by a modified Rankin score of two or less. Secondary endpoints included (1) improvement in NIHSS by four points from admission to discharge, (2) successful target artery recanalization, (3) the occurrence of symptomatic intracranial hemorrhage (ICH), and (4) all cause mortality at 90 days.
A total of 33 patients underwent emergency cerebral angiography for acute ischemic stroke, with 26 (79%) patients receiving CBT. Patients who did not receive CBT had no identifiable lesions on angiography, had lesions involving small vessels, which were deemed too distal for intervention, or were well collateralized. Patient demographics are presented in Table I. The most common reasons for not receiving intravenous thrombolysis included presentation later than 3 hr after symptom onset (52%), recent surgery (15%), and active bleeding (12%). Procedural characteristics are listed in Tables II and III. One-half of the patients received intra-arterial thrombolysis either alone or in conjunction with other devices.
|Age (mean)||62 ± 16.6|
|Coronary artery disease||12 (36)|
|Ejection fraction <40%||10 (30)|
|Atrial fibrillation||11 (33)|
|Atrial septal defect/patent foramen ovale||3 (9)|
|Previous TIA||11 (33)|
|Mean ± SD||16.1 ± 9.7|
|Intervention attempted||26 (79)|
|Contraindication to thrombolytic|
|presentation >3 hr from symptom onset||17 (52)|
|bleeding/recent surgery||9 (27)|
|Presentation time (min)a||168 ± 127|
|Fluoroscopy time (min)||20.1 ± 14.4|
|Mean contrast volume (ml)||202 ± 67|
|Middle cerebral artery||18 (55)|
|Basilar artery||5 (15)|
|Internal carotid artery||3 (9)|
|None identified||3 (9)|
|Ophthalmic artery||2 (6)|
|Vertebral artery||1 (3)|
|Anterior cerebral artery/Middle cerebral artery||1 (3)|
|MERCI device used||4 (15)|
|Intra-arterial thrombolysis||13 (50)|
|Glycoprotein IIb/IIIa receptor antagonist||0 (0)|
|Combined thrombolysis and device||6 (23)|
Successful “culprit” artery recanalization (≤50% residual stenosis with restoration of culprit artery flow, and without flow-limiting dissection or vessel perforation) was achieved in 23 (88%) of 26 patients. In-hospital adverse events occurred in 4 (15%) patients, with ICH (12%) being the most common (Table IV). The baseline NIHSS for patients who underwent CBT was 16.5 ± 9.9 (median 16) which improved significantly to 9.9 ± 8.7 (median 9) (P < 0.001) at discharge. An improvement in the NIHSS by four or more points during hospitalization was achieved in 18 (69%) of the 26 CBT patients. A modified Rankin score of 2 or less (indicating mild disability) was achieved in half (n = 13) of the patients treated with CBT (Table V). All cause mortality at 90 days was 8% (2 of 26).
|Intracranial hemorrhage||3 (12)|
|New ischemic stroke||1 (4)|
|Myocardial infarction||0 (0)|
|Successful reperfusiona||23 (88)|
|Reduction in NIHSS ≥4b||18 (69)|
|Mortality at 90 days||2 (8)|
|Modified Rankin ≤2 at 90 days||13 (50)|
Patients who had angiography without CBT had lower stroke acuity, with an average presenting NIHSS of 14.1 ± 12.1 (median 8), and only 2 (28.6%) of 7 had an improvement of 4 points or more in NIHSS at hospital discharge. Modified Rankin scores were available at 90 days in 5 (71%) of 7 patients, with 3 (60%) of 5 having a modified Rankin score of 2 or less.
We combined the outcomes of the present cohort with our previously published series of 16 CBT stroke patients . The combined group of 42 patients demonstrates favorable outcomes for functional status, morbidity, and mortality when compared with previously published trials (Table VI).
|Study||Patients||Age (years)||Male (%)||NIHSS baseline (median)||ICH symptomatic (%)||Mortality at 1–3 Mos (%)||mRankin ≤2 at 90 days (%)|
|NINDS||168||69||57||14||6.4||17 at 3 months||39a|
|STARS||389||69||55||13||3.3||13 at 1 month||43|
|IMS||80||18–80||50||18||6.3||16 at 3 months||43|
|IMS II||81||64||57||19||9.9||16 at 3 months||46|
|MERCI||151||67||54||20b||7.8||32 at 3 months||46|
|Multi-MERCI||164||68||43||19||9.8||34 at 3 months||36|
|EMS||17||66||53||16||11.7||29 at 3 months||33a|
|PROACT II||121||64||58||17||10||25 at 3 months||40|
|OCHSNER||42||64||44||16||12||9.5 at 1 month||45|
Our single center experience with a multidisciplinary approach to acute stroke intervention by interventional cardiologists in patients ineligible for intravenous thrombolysis has been encouraging. At our center, CBT is performed by interventional cardiologists with extensive carotid stenting experience who provide on-demand, 24 hr a day, year-round coverage for intracranial CBT . The use of intracranial angioplasty and stenting for acute stroke has been reported in case series with recanalization rates that approach 90% [25–27]. Our recanalization rate of 88%, using multiple modalities, mirror these data, which is notably higher than for intravenous thrombolysis administered within 3 hr of stroke onset or intra-arterial thrombolysis alone [10, 24]. Our data demonstrate the safety and efficacy of CBT in the hands of interventional cardiologists with carotid stent experience (in conjunction with stroke neurologists) for patients with acute stroke who are not eligible for intravenous thrombolysis. When combining this cohort of patients with our previously published data , our outcomes are very much in line with published trials (Table VI).
For patients with acute stroke presenting within 3 hr of symptom onset, without contraindications to intravenous thrombolytic therapy, there is randomized data supporting its effectiveness . However, intravenous thrombolysis is less effective in large intracerebral vessel occlusion (distal internal carotid artery or proximal MCA), where mechanical thrombectomy with or without intra-arterial thrombolysis achieves higher patency rates [10, 14, 28, 29]. Consistent with outcomes reported for acute myocardial infarction, early and successful recanalization of the stroke-related artery appears to correlate with improved clinical outcomes [13, 30–32]. However, late recanalization of intracranial vessels can be associated with hemorrhagic transformation (ICH) or severe cerebral edema, requiring that safety of reperfusion therapies be balanced with efficacy .
When compared with intravenous thrombolysis, CBT permits direct visualization of the infarct related vessel and assessment of the degree of collateral circulation to the jeopardized brain tissue. This allows tailoring of therapy to the location and characteristics of the lesion. Importantly, assessing the anatomy may lead to a decision not to intervene (as seen in 20% of the patients in our cohort), either due to adequate collateralization of the threatened region or very distal disease, which is not amenable to CBT. We believe the individualized treatment that can be offered with this approach optimizes patient outcomes and minimizes risk. CBT also has been successfully utilized in nonrandomized trials for artery recanalization up to 8 hr after stroke onset [13, 31], which is a significant advantage over intravenous thrombolysis therapy. Imaging-based criteria for selecting patients outside the 3-hr time window for intravenous thrombolysis using CT and MR-based perfusion imaging may allow for optimization of patient selection for CBT [34, 35].
In this series, we did not use a NIHSS cut-off value to select or exclude patients for CBT. Instead, strokes which were deemed disabling based upon symptoms, such as loss of vision or speech, were taken for emergent angiography and possible intervention even if the NIHSS was relatively low (<10). Of the 11 patients with presenting NIHSS ≤10, 7 (63%) underwent CBT, and 3 (43%) of those met the primary endpoint of a modified Rankin ≤2 at 90 days. This suggests that patients with relatively low NIHSS (despite significant neurologic deficits) likely benefit from CBT to nearly the same degree as those presenting with much higher NIHSS.
Ischemic stroke and acute myocardial infarction share many features . In both cases, the time to reperfusion is a crucial factor in determining outcome. For both, CBT is associated with higher (relative to intravenous thrombolysis) rates of recanalization (TIMI flow) and improved tissue reperfusion . Despite these similarities, there are important differences. The pathophysiology of ischemic stroke is more often embolic, whereas heart attacks typically result from in situ thrombosis because of plaque rupture . Bleeding into the brain (ICH) is more strongly associated with death  than intramyocardial hemorrhage. ICH is not rare following CBT, with symptomatic ICH rates of 3–12% across published trials [4, 13, 20, 24, 27]. Mortality at 3 months is markedly higher for stroke patients (17–32%) [4, 13] than the single digit mortality seen following hospital discharge for heart attack patients .
Treating acute stroke is not risk free, requiring that potential benefit be weighed against the expected complications. We found a combined rate of in-hospital adverse events of 15%, including a 12% rate of symptomatic ICH (Table III). However, the paucity of reperfusion options for these patients who are not candidates for intravenous thrombolytic therapy, and the poor outcomes associated with supportive care as demonstrated in the control arm of the NINDS , where only 3 of 10 patients had favorable neurologic outcomes at 6 months, encourages aggressive therapy for larger or disabling strokes.
Despite the benefits of reperfusion therapy in patients not eligible for intravenous thrombolysis, widespread adoption of CBT will require a dramatic increase in the number of physician-providers who can offer this service in communities across the country. A recent survey indicates that fewer than 400 neuroradiologists are practicing nationwide in the US, with five states having none . A national initiative to offer around-the-clock CBT for acute stroke cannot be sustained with so few providers. We believe that the national shortage of neuroradiologists may be reasonably augmented by the pool of physicians with carotid stent experience. Interventional cardiologists, vascular surgeons, interventional neurologists, and neurosurgeons with experience in carotid stenting are experienced in cerebral angiography, comfortable with cervical vessel cannulation, and are prepared to perform “neurorescue” should debris embolize during carotid intervention. As such, they are already performing acute stroke intervention and are a natural fit for expanding the workforce of qualified providers. Training guidelines for stroke interventionalists will need to be established by interdisciplinary cooperation and consensus.
The current national focus on minimizing door to balloon time for acute myocardial infarction is an excellent model for acute stroke therapy [33, 42, 43]. The treatment of acute stroke is facilitated by multidisciplinary participation, with every specialist offering their individual contribution to the total effort. Only through cooperative efforts, working together across traditional boundaries, can the necessary manpower requirement be met to provide around-the-clock access to acute stroke intervention. Patients with acute stroke would benefit from a national initiative to minimize “door to needle time” for stroke patients eligible for intravenous thrombolysis and “door to balloon time” for selected patients not eligible for intravenous thrombolysis.
Our study has several limitations. It is a retrospective, single center, nonrandomized trial with a small number of patients. The treatment strategy was not controlled or predetermined but was based on a multidisciplinary assessment of timing of the stroke onset, stroke size, severity of disability, angiographic lesion location, lesion morphology, and the presence of a collateral circulation. Nevertheless, because of the myriad combinations of presentations and treatment options, we believe that stroke therapy needs to be tailored to each patient's unique circumstances.
Our data suggest that CBT for severe, disabling acute stroke is an important and effective treatment for selected patients not eligible for intravenous thrombolysis. Unfortunately, the widespread applicability of a 24/7 treatment strategy in most communities is limited by a physician-provider manpower shortage. The “time is brain” paradigm requires that 24 hr a day, 365 days a year “CBT stroke teams” are available for patients with acute stroke who are not candidates for intravenous thrombolysis. To that end, it will be necessary to create multidisciplinary teams consisting of experienced carotid stent operators and stroke specialists to improve the quality of care and outcomes for patients presenting with acute stroke.
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