American Heart Association

Monthly Archives: February 2014

Poor functional outcome in young stroke patients aged 18-50 years.

Alireza Noorian, MD

Synhaeve NE, Arntz RM, Maaijwee NAM, Rutten-Jacobs LCA, Schoonderwaldt HC, Dorresteijn LDA, et al. Poor Long-Term Functional Outcome After Stroke Among Adults Aged 18 to 50 Years: Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation (FUTURE) Study. Stroke. 2014

Nearly 10% of all the strokes occur in the younger group of patients between 18-50 years. While the uncertainty about the functional outcome can affect the youth, their family and their future, few studies have addressed the longterm functional outcome in this group of patients.

As part of the “Follow-Up of Transient ischemic attack and stroke patients and Unelucidated Risk factor Evaluation”-study (FUTURE study), Synhaeve et al evaluated the longterm functional outcome in these patients after a TIA, Ischemic stroke and ICH. They demonstrated that over 9 years of follow up, about one out of 8 survivors with an ischemic stroke or ICH was functionally dependent. This number was one in 15 for TIA patients.

The factors affecting long-term functional outcome include age, severity of the initial stroke and the recurrence of stroke, stressing the importance of optimal preventive strategies in this population. Over this 30 year cohort, the more recently admitted patients had better outcome, reflecting the major improvements in stroke care and secondary prevention; Yet overall the prognosis after stroke in the youth remains poor.

By |February 27th, 2014|Uncategorized|1 Comment

NT-proBNP levels for stroke risk prediction in anticoagulated patients

Peter Hannon, MD

Roldán V, Antonio Vílchez JA, Manzano-Fernández S, Jover E, Gálvez J, Puche CM, et al. Usefulness of N-Terminal Pro–B-Type Natriuretic Peptide Levels forStroke Risk Prediction in Anticoagulated Patients With Atrial Fibrillation. Stroke. 2014

BNP levels have been shown in prior studies to have predictive value for atrial fibrillation. NT-proBNP is an inactive byproduct produced when cleaving BNP to its active form, and has been associated with an increased risk of morbidity and mortality in patients with and without cardiac disease. In this study, authors Roldán, et al have investigated the correlation of NT-proBNP levels with stroke, composite vascular events, and death in a population of patients with known afib, on anticoagulation (acenocoumarol), and with stable INRs (2-3, time in therapeutic range >70%).

1172 patients were included in the study with a mean age of 76. A CHA2DS2-VASc stroke risk score (median = 4) and HAS-BLED bleeding risk score was calculated at baseline, and patients were reassessed at a median follow-up of 1007 days. Primary end point was stroke or TIA, and secondary endpoints included a composite of cardiovascular events (stroke, TIA, systemic embolism, ACS, HF, cardiac death), as well as major bleeding and all-cause death.

On multivariate analysis, authors found that high NT-proBNP leves were significantly associated with poor prognosis, even after adjusting for the CHA2DS2-VASc score. A level of >822pg/nl had a HR of 2.71 for stroke; a level of >304 pg/nl had a HR of 1.85 for composite vascular events; and for all cause mortality an NT-proBNP level of >519pg/nl had a HR of 1.66. NT-proBNP levels did not predict increased bleeding risks.

Authors note limitations to this study, including the lack of a baseline echocardiogram, and that other factors such as age or renal dysfunction can affect NT-proBP levels. In this particular patient population, the big question is: how does this change management? Clearly, follow-up studies are needed. Do these results change at higher INR goals or on different oral anticoagulants? As more information in these areas come out in the future, it’s possible we may find NT-proBNP a useful tool in tailoring appropriate anticoagulation therapies to our patients.

By |February 26th, 2014|Uncategorized|0 Comments

Advanced CT imaging Linked with More Reperfusion Therapy in Acute Ischemic Stroke

Waimei Tai, MD

Vagal A, Meganathan K, Kleindorfer DO, Adeoye O, Hornung R, and Khatri P. Increasing Use of Computed Tomographic Perfusion and Computed Tomographic Angiograms in Acute Ischemic Stroke From 2006 to 2010. Stroke. 2014

Vagal et. al analyzed a large inpatient sample database to assess the utility of different CT based modalities for acute ischemic stroke. Not surprisingly it demonstrated a rise in advanced CT modality use (CT angiogram 3.8% in 2006 to 10.% in 2010, and CT perfusion use from 0.05% in 2006 to 2.9% in 2010). 
Similarly, reperfusion therapy also increased, although growth varied by subset of patients and availability of imaging information.

For head CT alone, iv tpa use went from 3% in 2006 to 4.7% in 2010, likely to systematic effects of education campaigns and the general improvement in stroke systems of care. For patients who received CT angiogram, iv tpa use went from 10.6 to 10.4%, not much of an increase right? This is because most people agree that the use of CT angiogram is not required for the iv tpa decision. While some centers (including my own) get CT angiogram as part of the initial stroke code evaluation, we don’t necessarily use it to make the iv tpa decision. It’s helpful for thrombectomy decisions.

But where the trends reverse is in thrombectomy: use of CT angiogram meant you were more likely to get mechanical therapy from 0.9% in 2006 to 3.7% in 2010, an almost 4 fold increase.  CT perfusion showed this trend as well, going from 3.7% in 2006 to 7.4% use in 2010 (2 fold increase). This intuitively makes sense, programs that use advanced modalities often have advanced acute stroke interventions as well (they study also looked at other indicators that could predicate use: academic centers , urban settings and larger hospitals which, not surprisingly have more imaging and more acute treatments) And as in my experience, lots of proceduralists want to know if there’s a clot to pull out before they go into an emergent procedure-and this is where the CT angiogram and perfusion offers additional data for decision making.

The bigger elephant in the room is: does the mechanical thrombectomy help in the long run? This has not been addressed in any definitive randomized trial (previous studies that did a not so good job with little imaging guided patient selection is not very convincing on this at all, hence all the fuss). What we do know is that in cohort based studies (DEFUSE2) patients appropriately selected (big penumbra, small ischemic core) do well. Another CT based cohort study is ongoing (NCT01622517) but I imagine that it will show a similar result: appropriately selected patients will respond will to reperfusion therapy.

But back to the study-since CT angiogram and perfusion and its anticipated consequence-more thrombectomy-hasn’t been demonstrated to work yet, why is there a trend in increased use?

Well, doctors like more data. And if they think it’ll help in decision making and it’s available and can be billed, why not use it? Well, for one reason: technology creepdefinitely plays a part in the ballooning price tags in healthcare. Not to mention that repeated use of radiation based diagnostic modalities carry their own risk. I think studies that are ongoing will hopefully shed some light on deciding when and where we should be using expensive diagnostic tests. Until then, I can only expect that if payors will pay, we will keep using it.
By |February 25th, 2014|Uncategorized|0 Comments

Serum Albumin, A Novel Biomarker for Cryptogenic Strokes and Paroxysmal Atrial Fibrillation?

Hassanain Toma, MD

Xu WH, Dong C, Rundek T, Elkind MSV, and Sacco RL. Serum Albumin Levels Are Associated With Cardioembolic and Cryptogenic Ischemic Strokes: Northern Manhattan Study. Stroke. 2014

The Northern Manhattan Study (NOMAS) is
 a prospective cohort study designed to determine stroke incidence, risk factors, and prognosis in a multiethnic urban population in northern Manhattan, NY. Xu, et al. investigated the association between serum albumin (SA) levels and ischemic stroke etiologies in this population. They stratified SA levels according to tertiles. Patients with serum albumin levels in the bottom tertile (2.7-4.2 g/dL) had an increased risk of all stroke (HR 1.76), ischemic stroke (HR 1.67), cardioembolic stroke (HR 1.92) and cryptogenic stroke (HR 2.59) than those within the top tertile (4.6-5.5 g/dL). However, SA levels were not associated with large vessel or lacunar stroke.

The authors demonstrated an association between low SA levels and ischemic strokes (cardioembolic and cryptogenic subtypes). This is interesting because Copenhagen City Heart Study and the Framingham offspring study reported an association between low SA and heart disease (atrial fibrillation, myocardial infarction, and heart failure). Could SA be the new biomarker for identifying patients at risk of cardioemblic stroke and cryptogenic strokes? I think it’s only a matter of time that someone decides to perform an individual patient-level data meta-analysis to better study this association.

In the meantime, I leave you with this thought: Would you anticoagulate cryptogenic stroke patients with low SA levels and a negative 30-days cardiac monitoring?

By |February 24th, 2014|Uncategorized|0 Comments

ASPECTS 0-4? Cath lab no more.

Nirali Vora, MD

Yoo A, O Zaidat O, Chaudhry Z, Berkhemer O, Ganzolez R, Goyal M, et al. Impact of Pretreatment Noncontrast CT Alberta Stroke Program Early CTScore on Clinical Outcome After Intra-Arterial Stroke Therapy. Stroke. 2014

How many times does early hypodensity or the ASPECTSscore on a patient’s CT influence your choice to pursue intra-arterial therapies? In the era post-IMS III, MR Rescue, and Synthesis, we are very careful to select the “right” patients for the cath lab. Ideally, a patient with a small infarct core (and larger mismatch) is the right patient, as evidenced by recently published DEFUSE 2. However, not all patients undergo acute MRI or perfusion imaging. Everyone does get a head CT and in those patients, where do you draw the line? Standard ASPECTS <7? ASPECTS <5?

Penumbra funded this pooled analysis of 249 patients treated with IA therapy from their single-arm Pivotal trial and post-marketing PICS registry. Yoo et al studied the relationship between modified ASPECTS score and functional independence at 90 days. Good outcomes were significantly less in ASPECTS 0-4 (5%) compared to 5-7 (38.6%) or 8-10 (46%).  One confounder was time to reperfusion, which was faster among those with better ASPECTS scores.  However, the authors report higher ASPECTs score independently predicted good outcome.

It’s hard to draw the firm conclusion that ASPECTS >5 will have good outcomes, since there was no control arm/study of patients who did not go on to IA therapy. However, I agree with the authors that this study further supports that we should NOT take patients with ASPECTS 0-4 to the cath lab due to poor outcomes (5% independent at 90 days and 55% mortality). 

Should ASPECTS 0-4 be a standard exclusion criteria in future IA studies? A quick glance at SWIFT PRIME’s exclusion criteria suggest it’s not at present. They are using the standard  >1/3 MCA territory exclusion.  Thought it’s cumbersome to ensure appropriate training, optimizing selection will be the cornerstone in the saga to prove IA therapy!

By |February 21st, 2014|Uncategorized|0 Comments

Multimodal MRI reveals targets for stroke rehabilitation

Matthew Edwardson, MD

Zhang J, Meng L, Qin W, Liu N, Shi FD, and Yu C. Structural Damage and Functional Reorganization in Ipsilesional M1 in Well-Recovered Patients With Subcortical Stroke. Stroke. 2014

The human brain undergoes significant plastic change after stroke, yet the details of how this occurs remain obscure. A better understanding of this process may allow us to amplify functional recovery using brain stimulation, pharmacologic manipulation, or even stem cell therapy. In lieu of peering directly into the brain of a living human, multiple MRI techniques including resting state fMRI have recently emerged. Zhang and colleagues used a multimodal MRI approach to better characterize functional reorganization in chronic stroke patients.

The authors studied 26 chronic subcortical stroke patients who had achieved either partial or complete motor recovery. They compared cortical thickness, task-related cortical activation in M1, amplitude of low-frequency fluctuations (ALFF), and resting state functional connectivity (rsFC) between the stroke patients and 25 age-matched healthy controls. They discovered that stroke patients had an area of decreased cortical thickness in lesional M1 that also showed increased task-related activation, ALFF and rsFC in comparison to control subjects. In addition, stroke patients had a separate area of lesional M1 with no cortical atrophy that demonstrated increased cortical activation, ALFF, and rsFC. Those with complete motor recovery had dramatically increased ALFF in these areas while those with partial recovery had an intermediate increase in ALFF.

Resting state fMRI is an emerging field that holds promise to help elucidate the subtleties of brain reorganization after stroke. Unlike task-related fMRI, which requires some form of motor movement, even severely disabled stroke patients can participate in resting state studies. In general, functional connectivity decreases immediately after stroke then gradually returns to normal or slightly increased levels in those with good recovery. The ALFF also comes from resting state fMRI data. Though poorly understood, ALFF is thought to represent spontaneous regional neuronal activity in the resting state as opposed to connectivity. The findings in the current study, showing progressively increasing levels of ALFF depending on the state of recovery, suggest ALFF may emerge as an important imaging biomarker for stroke recovery. The next step would entail proving this in a follow up longitudinal study. Such an imaging biomarker would provide targets for focal brain stimulation and other rehabilitation strategies. The authors have shed light on how various MRI approaches characterize neural reorganization after stroke. Now we need to translate these findings into better therapies for our patients.

By |February 20th, 2014|Uncategorized|0 Comments

Are implantable monitors a crystal ball for detecting afib? Preliminary Crystal AF results from ISC

International Stroke Conference (ISC)
February 12-14, 2014

Just announced at ISC 2014 were the industry-sponsored Crystal-AF results by Rich Bernstein et al which REVEALed implantable cardiac monitoring at 6 months detected atrial fibrillation at least 6 times more often than conservative workup with shorter term monitoring.

Should I be increasing my use of these devices? Only a small percentage of patients had complications with pocket site infections; it seems harmless enough. I have actually never ordered implantable cardiac monitoring. I go for a simple 21 day Holter (or at our institution
14 day Ziopatch). Perhaps, implantable monitoring is a good option if you have a high suspicion for cardioembolic stroke and your non-invasive monitoring does not work after the first several weeks.

Several questions remain. The incidence of afib was relatively low. The definition of afib was greater than 30 seconds of irregular rhythm without p waves. Why 30 seconds? How many of you in practice initiate anticoagulation only if a certain duration of afib detected? I learned
that a few good seconds of afib was all I needed!

How long should the monitoring go on? This particular device is good for up to 3 years. The secondary outcomes showed increased detection with increased duration if monitoring, suggesting one can leave it in up to 3 years until you find afib.

I eagerly await the formal publication of results, and the community’s response: will you change your practice? 

Take this anonymous poll and see what others think. 


– Nirali Vora, MD

By |February 19th, 2014|Conference|0 Comments

Identifying and treating paroxysmal atrial fibrillation: Many questions still remain- A report from the ISC

International Stroke Conference (ISC)
February 12-14, 2014

Paroxysmal atrial fibrillation (PAF) is an elusive cause of stroke, but because anticoagulation is an effective intervention to prevent recurrent stroke in patients with AF, it is important to diagnose it. While most stroke patients undergo telemetry monitoring for several days during the acute stroke admission, PAF is not always detected, and long-term outpatient cardiac monitoring has been proposed as an important element in the evaluation of stroke etiology. Several studies presented at this year’s ISC looked at the issue, and while they shed some light on the issue, many questions still remain.

Two studies that used mobile cardiac outpatient telemetry (MOCT) for 25-28 days in patients with cryptogenic stroke found an incidence of PAF in 13%. Investigators in both studies looked for imaging and echocardiographic fetures that could identify patients who were most likely to benefit from MOCT. Among 132 patients (mean age 72 years), Omar Kass-Hout and his group from Emory University found that cortical lesions on MRI and higher mean left atrial diameter, lower tissue Doppler velocity, and higher left atrium volume index (LAVI) and mean LAVI/late diastolic Doppler velocity on echocardiography were associated with a diagnosis of PAF. Scott Kasner and colleagues at the University of Pennsylvania retrospectively analyses data from 227 patients (mean age 62 years). They did not find any echocardiographic factors associated with incident PAF (they only looked at 4 factors: LA size, ejection fraction, aortic arch atheroma and PFO) but noted that age >60 years and a prior infarct, particularly cortical or cerebellar, were associated with PAF on MOCT. It is possible that the Emory group had the echocardiographic associations because the patients were older or because the investigators looked at many more factors (repeat testing).

While Kass-Hout and Kasner studied patients with cryptogenic stroke, it is possible that MCOT should not be limited to patients with stroke of undetermined etiology. Some patients may have more than one potential cause for the stroke (vascular diseases tend to go together), and some question whether all patients should be evaluated with MOCT, independent of alternative identified etiologies. Dr. Ghazala Basir and her colleagues from the University of Alberta favor this approach because they found, in a study of 96 patients who had MOCT for 3 weeks, that 32% of those with cryptogenic stroke and 36% of those with other potential etiologies had PAF.

While looking for PAF using MOCT is an attractive strategy, several questions remain unanswered. Are the implications (in terms of stroke risk) of finding PAF on MOCT similar to those of chronic AF, as suggested by a study presented by Seiji Miura and colleagues from Kyushu Medical Center in Japan? Are all episodes of PAF equally embologenic, independent of duration? Rolf Watcher and colleagues from the University of Mainz in Germany compared the stroke severity among patients with different duration of PAF and found that patients with paroxysmal AF of at least 30 seconds during 7-day-Holter have strokes similar to patients with persistent AF. It is unclear whether runs of PAF shorter than 30 seconds confer an increased stroke risk.

While these studies tell us about the prevalence of PAF in patients with stroke, we do not know the baseline prevalence of PAF among patients without stroke, or even without vascular risk factors, and it is thus difficult to place the rates in these studies in context. We also do not know whether anticoagulants have a similar risk-benefit profile in patients with chronic AF and with PAF. DO we need a clinical trial to evaluate whether anticoagulation is warranted in these patients?

– José G. Merino
By |February 18th, 2014|Conference|0 Comments

So you can manage adults with TIA. What about children?

Seby John, MD

Adil MM, Qureshi AI, Beslow LA, and Jordan LC. Transient Ischemic Attack Requiring Hospitalization of Children in the United States: Kids’ Inpatient Database 2003 to 2009. Stroke. 2014

What if a child presents to you with a TIA.  Do you have an ABCD like risk stratification score you can use? Do you observe, admit or discharge the patient? What risk factors do you evaluate for?  If your patient was an adult, you would readily have answers for most of these questions. Unfortunately, they do not apply to children. The recent years have seen more focus on pediatric ischemic stroke, but there is sparse data on TIA.

In this paper, Adil and colleagues attempt to understand the prevalence and risk factors associated with TIA. They used the national Kid’s Inpatient Database to identify children aged 1-18 years who were admitted with a diagnosis of TIA in 2003, 2006 and 2009. ICD-9 codes were used to identify these admissions, and record other secondary diagnoses. During this time, 531 children were admitted with TIA with two-thirds being adolescents aged 11-18. Important secondary diagnosis included sickle cell disease, congenital heart disease, moyamoya, recent stroke and migraine. Close to 40% had no risk factors identified. Traditional adult risk factors such as hypertension, diabetes and coagulopathy were rarely found.

Although this study has the obvious limitations of using a national database, it provides a glimpse of the problem. Compared to TIA, there were 5 times as many admissions for ischemic stroke during the same timeframe. Keep in mind though that TIAs in children aren’t as straightforward to diagnose, and it is likely that many were missed or misdiagnosed. Important questions regarding risk of subsequent stroke is difficult to determine but 4% also had a diagnosis code for stroke during the same hospitalization. Despite such dearth of knowledge, it is reassuring that none of the children died and 97% were discharged home. This of course should be no reason for complacency, and further study to identify risk factors, subsequent stroke risk and appropriate management should be pursued aggressively.
By |February 14th, 2014|Uncategorized|0 Comments

Carotid plaque pathology: a tool for stroke therapy?

Nirali Vora, MD

Marnane M, Prendeville S, McDonnell C, Noone I, Barry M, Morgan Crowe, et al. Plaque Inflammation and Unstable Morphology Are Associated With Early Stroke Recurrence in Symptomatic Carotid Stenosis. Stroke. 2014.

We recommend carotid endarterectomy (CEA) in symptomatic, high-grade carotid stenosis to avoid a high risk of early, recurrent stroke. What do those arteries and the plaque look like under the microscope? Can the pathology clue us into better medical therapies for stroke prevention?

Marnane et al. attempted to answer this question by reviewing the histopathology of carotid plaque resected during CEA in patients who had recently had a TIA or stroke.  They had a small population of 44 patients with typical distribution of vascular risk factors and symptomatic carotid stenosis, with the majority high-grade >70% stenosis. Stroke recurrence prior to CEA occurred among 27% patients. All strokes were confirmed with DWI positivity on MRI. CEA took place within a mean of 10 days from most recent event. 

Among patients who had recurrent stroke between initial presentation and CEA (versus those that simply had a single event), the plaque had significantly increased inflammation with denser macrophages and lower fibrous tissue content. This was true even when adjusting for age or severity of carotid stenosis.

It’s unclear to me if this association is the result of the recurrent stroke or an underlying feature of plaque in high-risk carotids?  Either way, it seems reasonable to target therapy with drugs that can reduce macrophage infiltration. Traditionally, we think of statin therapy as having some “anti-inflammatory” effect. The patients in both arms did receive equal amount of statins (and anti platelets). What is another therapy we can use to target this macrophage inflammation, either acutely or for prevention? Let us know what you are studying!  
By |February 12th, 2014|Uncategorized|0 Comments