Arturo Tamayo

Effects of Intensive Medical Therapy on Microemboli and Cardiovascular Risk in Asymptomatic Carotid Stenosis

OBJECTIVE To assess the effect of more intensive medical therapy on the rate of transcranial Doppler (TCD) microemboli and cardiovascular events in patients with asymptomatic carotid stenosis (ACS). DESIGN A prospective study. SETTING A teaching hospital. PATIENTS Four hundred sixty-eight patients with ACS greater than 60% by Doppler peak velocity. MAIN OUTCOME MEASURES We compared (1) the proportion of ACS patients who had microemboli on TCD, (2) cardiovascular events, (3) rate of carotid plaque progression, and (4) baseline medical therapy, before and since 2003. RESULTS Among 468 ACS patients, 199 were enrolled between January 1, 2000, and December 31, 2002; and 269 were enrolled between January 1, 2003, and July 30, 2007. Microemboli were present in 12.6% before 2003 and 3.7% since 2003 (P < .001). The decline in microemboli coincided with better control of plasma lipids and slower progression of carotid total plaque area. Since 2003, there have been significantly fewer cardiovascular events among patients with ACS: 17.6% had stroke, death, myocardial infarction, or carotid endarterectomy for symptoms before 2003, vs 5.6% since 2003 (P < .001). The rate of carotid plaque progression in the first year of follow-up has declined from 69 mm(2) (SD, 96 mm(2)) to 23 mm(2) (SD, 86 mm(2)) (P < .001). CONCLUSIONS Cardiovascular events and microemboli on TCD have markedly declined with more intensive medical therapy. Less than 5% of patients with ACS now stand to benefit from revascularization; patients with ACS should receive intensive medical therapy and should only be considered for revascularization if they have microemboli on TCD.

3D Ultrasound Measurement of Change in Carotid Plaque Volume A Tool for Rapid Evaluation of New Therapies

Background and Purpose— New therapies are being developed that are antiatherosclerotic but that lack intermediate end points, such as changes in plasma lipids, which can be measured to test efficacy. To study such treatments, it will be necessary to directly measure changes in atherosclerosis. The study was designed to determine sample sizes needed to detect effects of treatment using 3D ultrasound (US) measurement of carotid plaque. Methods— In 38 patients with carotid stenosis >60%, age±SD 69.42±7.87 years, 15 female, randomly assigned in a double-blind fashion to 80 mg atorvastatin daily (n=17) versus placebo (n=21), we measured 3D plaque volume at baseline and after 3 months by disc segmentation of voxels representing carotid artery plaque, after 3D reconstruction of parallel transverse duplex US scans into volumetric 3D data sets. Results— There were no significant differences in baseline risk factors. The rate of progression was 16.81±74.10 mm3 in patients taking placebo versus regression of −90.25±85.12 mm3 in patients taking atorvastatin (P<0.0001) Conclusions— 3D plaque volume measurement can show large effects of therapy on atherosclerosis in 3 months in sample sizes of ≈20 patients per group. Sample sizes of 22 per group would be sufficient to show an effect size of 25% that of atorvastatin in 6 months. This technology promises to be very useful in evaluation of new therapies.

Absence of Microemboli on Transcranial Doppler Identifies Low-Risk Patients With Asymptomatic Carotid Stenosis

Background and Purpose— Carotid endarterectomy clearly benefits patients with symptomatic severe stenosis (SCS), but the risk of stroke is so low for asymptomatic patients (ACS) that the number needed to treat is very high. We studied transcranial Doppler (TCD) embolus detection as a method for identifying patients at higher risk who would have a lower number needed to treat. Methods— Patients with carotid stenosis of ≥60% by Doppler ultrasound who had never been symptomatic (81%) or had been asymptomatic for at least 18 months (19%) were studied with TCD embolus detection for up to 1 hour on 2 occasions a week apart; patients were followed for 2 years. Results— 319 patients were studied, age (standard deviation) 69.68 (9.12) years; 32 (10%) had microemboli at baseline (TCD+). Events were more likely to occur in the first year. Patients with microemboli were much more likely to have microemboli 1 year later (34.4 versus 1.4%; P<0.0001) and were more likely to have a stroke during the first year of follow-up (15.6%, 95% CI, 4.1 to 79; versus 1%, 95% CI, 1.01 to 1.36; P<0.0001). Conclusions— Our findings indicate that TCD− ACS will not benefit from endarterectomy or stenting unless it can be done with a risk <1%; TCD+ may benefit as much as SCS if their surgical risk is not higher. These findings suggest that ACS should be managed medically with delay of surgery or stenting until the occurrence of symptoms or emboli.

High-risk asymptomatic carotid stenosis: Ulceration on 3D ultrasound vs TCD microemboli

Objective: We compared microemboli on transcranial Doppler (TCD) with carotid ulcerations on 3D ultrasound (US) as an additional method for identifying the small proportion of patients with asymptomatic carotid stenosis (ACS) who can benefit from revascularization such as endarterectomy or stenting. Methods: Patients with ACS (n = 253) with carotid stenosis >60% by Doppler ultrasound were studied prospectively with TCD embolus detection and 3D US to detect ulcers (the total number of ulcers in both internal carotids) and followed for 3 years. Results: Mean age was 69.66 (SD 8.51) years; 11 (4%) had ≥3 ulcers (Ulcer 3), 11 (6%) had microemboli, and 25 (10%) had microemboli or ≥3 ulcers. Ulcer 3 patients were more likely to have a stroke or death in 3 years (18% vs 2%; p = 0.03), regardless of the side on which the ulcers were found. The 3-year risk of stroke or death was 20% with microemboli vs 2% without (p = 0.003). The annual rate of ipsilateral stroke was 0.8%. Conclusion: Adding 3D US detection of ulcers doubles (to 10%) the proportion of patients with ACS who may benefit from endarterectomy or stenting. However, until 3-year event rates of stroke or death with endarterectomy or stenting reach <2%, 90% of patients with ACS would be better treated medically until they develop symptoms, ulcers, or emboli. Neurology® 2011;77:744–750

Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism.

BACKGROUND Patent foramen ovale (PFO) is an independent risk factor for cerebral infarction. Since ~25% of the population have a PFO, the simple association of PFO with stroke is not enough to establish the diagnosis of paradoxical embolism. We evaluated possible clinical clues to the diagnosis of paradoxical embolism. METHODS Among patients with cryptogenic ischemic stroke (CS) who were investigated for a right-to-left shunt (RLS), we compared clinical, coagulation and biochemical parameters in patients with PFO versus without PFO. RESULTS Among 1689 new patients referred for TIA/non-disabling stroke between 2001 and 2007, 175 with cryptogenic stroke (CS) were investigated for RLS by transcranial Doppler (TCD) bubble studies; 89 (5.5%) with positive TCD had a PFO confirmed by TEE. In multivariate logistic regression, a history of DVT or pulmonary embolism (OR, 4.39; 95% CI, 1.23-15.69; p=0.023), prolonged travel (OR, 8.77; 95% CI, 1.775-43.3; p=0.008) , migraine (OR, 2.30: 95% CI, 1.07-4.92; p=0.031), a Valsalva maneuver preceding the onset of focal neurological symptoms (OR, 3.33; 95% CI, 1.15-9.64; p=0.026) and waking up with stroke/TIA (OR, 4.53, 95% CI, 1.26-16.2; p=0.018) were independently associated with PFO-associated cerebrovascular events. Patients with PFO had higher plasma total homocysteine levels than patients without PFO (8.9+/-3 versus 7.9+/-2.6 micromol/L respectively; p=0.021). CONCLUSIONS A history of DVT or pulmonary embolism, migraine, recent prolonged travel, sleep apnea, waking up with TIA or stroke or a Valsalva maneuver preceding the event are clinical clues to the diagnosis of paradoxical embolism among patients with CS.

ASPECT scoring to estimate >1/3 middle cerebral artery territory infarction.

PURPOSE To compare the inter-observer reliability of Alberta Stroke Programme Early CT Scoring (ASPECTS) with the ICE (Idealize-Close-Estimate) method of estimating > 1/3 middle cerebral artery territory (MCAT) infarction amongst stroke neurologists and to determine how well ASPECT Scoring predicts > 1/3 MCAT infarctions in acute ischemic stroke (AIS). BACKGROUND The European Cooperative Acute Stroke Study suggested that > 1/3 involvement of the MCAT on early CT scan was a risk factor for symptomatic intracerebral hemorrhage (SICH) following treatment with tissue plasminogen activator (tPA) for AIS but, in the absence of a systematic method of estimation had poor interobserver reliability (Kappa 0.49). The ICE method was developed to standardize the approach to estimating early MCAT infarct size and has very good interobserver reliability (Kappa 0.72). ASPECTS has comparable interobserver reliability and is reported to predict both neurological outcome and SICH. METHODS Five stroke neurologists were tested with 40 AIS CT scans. Each performed blinded independent assessments of early ischemic changes with both ASPECTS and ICE. The reference standard was majority opinion of 1/3 MCAT determination of five neuroradiologists. A receiver operator curve (ROC) was constructed and likelihood ratios (LR) were calculated. Chance corrected agreement (kappa) and chance independent agreement (phi) were calculated for both methods, and analysis of variance was used to calculate reliability by intraclass correlation coefficient (ICC) for ASPECTS. RESULTS The LR for a positive test (> 1/3 MCAT) were extremely large and conclusive (approaching infinity) for ASPECTS of 0-3; were large and conclusive (30, 20, and 10) for ASPECTS of 4, 5, and 6 respectively; was an unhelpful 1 for ASPECTS of 7, and were again extremely large and conclusive (approaching zero) for ASPECTS of 8-10. A ROC plot supported an ASPECTS cutoff of < 7 as best for 1/3 MCAT estimation (94% sensitivity and 98% specificity). Kappa and Phi statistics were moderately good for both ASPECTS and ICE (0.7). ICC for ASPECTS was 0.8. CONCLUSIONS When experienced stroke neurologists utilize a formalized method of quantifying early ischemic changes on CT, either ASPECTS or ICE, the interobserver agreement and reliability are satisfactory. ASPECTS allows for a strong and conclusive estimation of the presence of 1/3 MCAT involvement and a cutoff point of < 7 results in best test performance.

Improved outcomes in stroke thrombolysis with pre-specified imaging criteria.

BACKGROUND A 1995 National Institute of Neurological Disorders (NINDS) study found benefit for intravenous tissue plasminogen activator (tPA) in acute ischemic stroke (AIS). The symptomatic intracranial hemorrhage (SICH) rate in the NINDS study was 6.4%, which may be deterring some physicians from using this medication. METHODS Starting December 1, 1998, patients with AIS in London, Ontario were treated according to NINDS criteria with one major exception; those with approximately greater than one-third involvement of the idealized middle cerebral artery (MCA) territory on neuroimaging were excluded from treatment. The method used to estimate involvement of one-third MCA territory involvement bears the acronym ICE and had a median kappa value of 0.80 among five physicians. Outcomes were compared to the NINDS study. RESULTS Between December 1, 1998 and February 1, 2000, 30 patients were treated. Compared to the NINDS study, more London patients were treated after 90 minutes (p<0.00001) and tended to be older. No SICH was observed. Compared to the treated arm of the NINDS trial, fewer London patients were dead or severely disabled at three months (p=0.04). Compared to the placebo arm of the trial, more patients made a partial recovery at 24 hours (p=0.02), more had normal outcomes (p=0.03) and fewer were dead or severely disabled at three months (p=0.004). CONCLUSIONS The results of the NINDS study were closely replicated and, in some instances, improved upon in this small series of Canadian patients, despite older are and later treatment. These findings suggest that imaging exclusion criteria may optimize the benefits of tPA.

Rapid Assessment and Treatment of Transient Ischemic Attacks and Minor Stroke in Canadian Emergency Departments: Time for a Paradigm Shift.

A majority of acute cerebrovascular syndromes are transient ischemic attacks (TIA) or minor ischemic strokes. They are often thought of and managed as though benign, but are in fact a warning of impending disabling stroke. The risk of stroke progression or recurrence is highest in the first hours to days from initial symptom onset, with a 6.7% risk at 48 hours and a 10% risk by 7 days after a TIA.1,2 The highest risk period is early, with a median time to a recurrence or progression event of 1 day; many events occur overnight after the initial ictus.3 Many strokes are preventable after a TIA. Rapid diagnosis and treatment reduces the risk of stroke by as much as 80%4,5 and significantly reduces mortality, long-term disability, and costs.6,7 The estimated annual cost avoidance in Canada from the rapid assessment and treatment of TIA is

Diabetes, Intracranial Stenosis and Microemboli in Asymptomatic Carotid Stenosis

313.8 million (of which

Canadian stroke best practice recommendations: Secondary prevention of stroke, sixth edition practice guidelines, update 2017:

269.2 million are indirect costs).8 To be most effective, the diagnosis and treatment of all TIAs and minor strokes must recognize the natural biology of the condition and should ideally occur on the same day as the event. Currently, this is not consistently achieved in Canada. There are several overlapping challenges with TIA/minor stroke management, including (1) establishing an accurate diagnosis of brain ischemia quickly; (2) establishing accurate triage approaches to risk-stratify patients; and (3) establishing systems of care that expedite both the diagnostic evaluation and initiation of treatment. Rapid access to both brain and vascular imaging is a unifying component of the solution to all these challenges. The clinical diagnosis of TIA/minor stroke is not always straightforward because a …