American Heart Association

Monthly Archives: September 2015

Serum leptin is not associated with stroke risk.

 
Dr. Saber and colleagues examine the longitudinal association between serum leptin levels and incident stroke in older individuals in the Framingham Heart Study.

The authors cite evidence for leptin as having a role in multiple metabolic processes, inflammation and platelet aggregation. It also seems that leptin has been variably associated with MI risk but also protection from coronary disease. Their purpose was to add to the small number of existing, limited studies exploring the relationship between leptin and stroke.


757 patients (mean age 79, 470 women) recruited from 1992 to 1994 were included and followed for incident stroke for up to 10 years. There were 119 strokes, of which 99 were ischemic. Atrial fibrillation was not a well-established stroke risk factor at that time, so baseline vascular risk factor covariates were limited to age, sex, systolic blood pressure, anti-hypertensive therapy, smoking status, diabetes and cardiovascular disease. Dyslipidemia was not included, either.

Multivariate Cox regression tested the relationship between sex-standardized log-leptin levels (to account for right-shifted distribution) and incident stroke. There was no association between baseline leptin and incident stroke or ischemic stroke. In patients with high waist-to-hip ratios, there was an inverse relationship between baseline leptin and stroke risk.

Their findings are consistent with two recent prospective studies. As they state, the observed inverse association between leptin and stroke risk in the highest waist-to-hip ratio subjects is intriguing. However, it is challenging to draw any mechanistic or clinical conclusions from this data except that serum leptin does not appear to be associated with stroke risk. Overall, leptin does not seem to be a reliable marker of cardiovascular or cerebrovascular risk.

Perfusion imaging can identify mismatch in acute ischemia leading to favorable outcomes following endovascular reperfusion

Jay Shah, MD

Albers GW, Goyal M, Jahan R, Bonafe A, Diener HC, Levy EI, et al. Relationships Between Imaging Assessments and Outcomes in Solitaire With the Intention for Thrombectomy as Primary Endovascular Treatment for Acute Ischemic Stroke. Stroke. 2015
 
Patients with target mismatch (TMM) have relatively small ischemic core with substantially larger region of critical hypoperfusion and have strong association between early reperfusion and favorable clinical outcomes. SWIFT PRIME was a randomized trial evaluating treatment with intravenous tPA versus tPA plus endovascular therapy. Brain imaging was primarily accomplished by CT perfusion. The authors in this study evaluated relationships between baseline and follow-up imaging and clinical outcomes. Ischemic core and hypoperfusion volumes were calculated and patients were stratified as either TMM or malignant profile. Imaging, typically MRI, was obtained at 27 hours to calculate infarct volume.

 
196 patients were enrolled in SWIFT PRIME and 166 had baseline perfusion imaging. 141 patients had the TMM profile while 25 did not. There was a potent relationship between 27-hour infarct volumes and clinical outcomes. Expectedly, results demonstrated progressively larger infarcts with modified rankin scale increase. Patients with TMM profile had significantly higher rates of reperfusion, smaller infarct volumes, and higher rates of functional independence at 3 months in the intervention group. In the malignant group, functional independence rates were 10% lower compared to rates in TMM group.

Results indicate that patients with TMM profile have favorable response to endovascular therapy on both clinical and imaging outcomes. As endovascular therapy becomes readily available, judicious patient selection will be important. As this study suggests, CT perfusion can be utilized to select patients with the favorable TMM profile. However, a limitation to this approach could be the potential unavailability of performing perfusion imaging at all hours and may lead to delays in thrombolytic and/or endovascular therapy. Interestingly, timing was monitored in SWIFT PRIME and perfusion imaging did not delay time to femoral puncture. It is also important to note that due to the low number of patients with malignant profile, the study was not powered to assess this population. Therefore, it would be premature to conclude that this group has inadequate response to endovascular therapy. Further studies are required to appropriately assess this subgroup.

By |September 29th, 2015|treatment|0 Comments

MALCOLM: Identifying a maximum core lesion threshold in patients undergoing endovascular therapy


Large infarct size has traditionally been a relative contraindication to endovascular therapy; previous studies have reported poorer outcomes in stroke patients with large lesion size and patients with large infarct size have typically been excluded from clinical studies. Recently, Gilgen, et al. published a study in Stroke which suggested that treating large DWI lesions with thrombectomy still confer a benefit, especially in younger patients; however, what still remains unclear is how large is too large. Here, the authors aimed to determine whether the admission infarct volume is predictive of the final infarct volume and to establish the maximum admission core lesion compatible with favorable outcome (MALCOLM), above which the probability of modified Rankin scale (mRS) 0-2 is < 10% for use as a selection tool in endovascular therapy.

 

Baseline admission infarct volume was calculated on the basis of DWI lesion on MRI (MRI-DWI) or CBV (cerebral blood volume) on CT perfusion (CTP) and compared to final infarct volume as measured on 24-48 hour post-admission non contrast CT scan. 29 patients were evaluated using MRI and 28 patients were evaluated using CTP. Infarct growth was smaller if recanalization was achieved, with lower final infarct volumes following successful recanalization. The authors identified a MALCOLM score of 39 ccs – when recanalization was successful, up to 64% of patients within MALCOLM had a favorable outcome as defined by mRS 0-2; even when recanalization was successful, in patients above MALCOLM, only 12% had a good outcome. The only predictor of favorable outcome was an admission core lesion below MALCOLM. Patients older than age 80 had a lower MALCOLM (15 ccs) compared to younger patients (40 ccs), and a higher MALCOLM was seen on CTP (42 ccs) compared to MRI-DWI (29 ccs).

There are still further studies that will need to be done in this field to address specifics, such as the differences between CTP and MRI-DWI, and whether there are other sequences within CTP which might more accurately estimate initial core volume, but identifying MALCOLM serves to potentially separate out which patients would most benefit from thrombectomy and which would not, putting us closer to answering the question posed previously, “how large is too large?”


MPRAGE – All the Rage for Identifying Basilar Intraplaque Hemorrhage

Ilana Spokoyny, MD

Yu JH, Kwak HS, Chung GH, Hwang SB, Park MS, and Park SH. Association of Intraplaque Hemorrhage and Acute Infarction in Patients With Basilar Artery Plaque. Stroke. 2015 

Atherosclerosis is a common cause of stroke, and while imaging has previously focused on the quantitative aspects (how stenotic is the vessel), we are now able to and thus interested in characterizing the more qualitative aspects of the plaque. In atherosclerotic plaques, intraplaque hemorrhage (IPH) is commonly seen and is thought to represent rupture of friable plaque vessels. In carotid plaques, IPH is associated with instability and rapid progression of plaque size and luminal stenosis. There has been recent research showing that IPH in the MCA (based on T-1 sequence hyperintensity) is associated with a risk of ipsilateral stroke. This has not yet been evaluated in basilar plaques, and is what the authors of this paper set out to do. 

The T-1 sequence MPRAGE (magnetization prepared rapid acquisition with gradiant-echo) has been shown to be more sensitive and specific for the identification of IPH than conventional T-1 or time-of-flight (TOF) MRA. In this study, to be considered “high signal” on MPRAGE, the area in question was required to be at least 150% of the signal intensity of the adjacent muscle.

Over a 3 year period, patients who had at least 50% basilar stenosis on TOF MRA and who consented to participate were enrolled in the study. These patients were identified either because of acute stroke code activation, or presentation with neurologic complaints such as dizziness, headache, giddiness, or vertigo. The High-Res MRI (including MPRAGE) was performed within two weeks of the initial qualifying MRI/MRA scan. To be considered “symptomatic”, the MRI had to show ischemic stroke (high DWI, low ADC signal) in the basilar artery territory (implying the stroke occurred within the last week). Those patients with > 50%stenosis in one or both vertebral arteries, less than 50% basilar stenosis, or non-atherosclerotic etiology (dissection, moyamoya) were excluded.

Of 73 patients, 45 were symptomatic and 28 were asymptomatic. MPRAGE demonstrated IPH in 54.5% of symptomatic patients, and only 20% of asymptomatic patients. Overall, 30 patients were MPRAGE positive (for IPH) and 43 were MPRAGE negative. The imaging-positive and imaging-negative patients did not differ on baseline characteristics, except for presence of symptomatic lesion (80 vs. 49%, RR 1.64, p<0.01) and degree of stenosis (73 vs. 62%, p<0.001). The sensitivity and specificity of IPH on MPRAGE for predicting stroke were 46.5% and 80%, respectively.

The prevalence of basilar IPH was higher than the prevalence reported in MCA plaques, maybe because the basilar is easier seen on axial imaging due to larger wall area, and maybe because the imaging technique was more sensitive (MPRAGE vs. standard T-1 MRI). The authors point out the limitation of not having a histologic gold standard; however, they reference a study which compared MRI imaging to histology and determined that MPRAGE was better than T-1 Fast Spin Echo or TOF at detecting and quantifying IPH.

My only concern is that the High-Res MRI (with MPRAGE) was done up to 2 weeks following the original MRI, and the original MRI may have been up to one week post-stroke in symptomatic patients. It would be very interesting to follow the asymptomatic patients (who still had >50% basilar stenosis) with serial MPRAGE MRIs, to determine if those with IPH versus those without had higher rates of stroke, whether a certain degree of IPH can predict cerebrovascular events, and whether IPH appears following a cerebrovascular event in previously imaging-negative patients.​

Cerebral venous thrombosis may be associated with anemia.

Russell Mitesh Cerejo, MD

Coutinho JM, Zuurbier SM, Gaartman AE, Dikstaal AA, Stam J, Middeldorp S, and  Cannegieter SC. Association Between Anemia and Cerebral Venous Thrombosis: Case–Control Study. Stroke. 2015
 
In the paper titled “Association between anemia and cerebral venous thrombosis (CVT): a case-control study”, Jonathan Coutinho and colleagues set out to evaluate the association of CVT and anemia. They evaluated 156 cases at their institution between 2006 and 2004 and compared their characteristics to 2916 controls, which were taken from the Dutch MEGA study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis) from 1999 to 2004.


Mean hemoglobin concentration was lower in cases than in controls (8.06 vs. 8.68 mmol/l, p<0.001). Anemia was present in 27.0 % (41/152) of the cases, significantly more frequently than in controls (6.5%, 189/2916; absolute difference 20.5%, 95% CI 14 – 28%). Patients with CVT more often had been diagnosed with cancer (9.2 vs. 3.7%) compared to controls (table 1). Oral contraceptive use (69.7% vs. 21.1%) and pregnancy/puerperium (5.3 vs. 1.4%) were more frequent in female cases. After adjustment for potential confounders, anemia was significantly associated with CVT (adjusted OR 4.4, 95% CI 2.8-6.9). Exclusion of patients with a recent infection, neurosurgical intervention, or inflammatory bowel disease, did not change the results (adjusted OR 3.9, 95% CI 2.4-6.4). When they excluded patients with a history of malignancy, the association between anemia and CVT remained significant (adjusted OR 3.6, 95% CI 2.2- 5.9). They also found that anemia is a stronger risk factor for CVT in men than in women.

This study sheds light on the possible association between CVT and anemia, which have been reported in prior case reports and small case series. However any causal correlations are difficult to extrapolate from this data. None the less this important association may be useful in monitoring patients at higher risk for CVT.

Cognitive Decline Occurs in More Than 1/3 of Long-Term Survivors of ICH

Alexander E. Merkler, MD

Benedictus MR, Hochart A, Rossi C, Boulouis G, Hénon H, van der Flier WM, and  Cordonnier C. Prognostic Factors for Cognitive Decline After Intracerebral Hemorrhage. Stroke. 2015

The association between stroke and cognitive decline is complex and, as Drs. Benedictus et al point out, pre-existing dementia is often present in patients with stroke, and post-stroke dementia is also highly prevalent. Furthermore, dementia increases the risk of stroke, and as a corollary, stroke also increases the risk of dementia. Disentangling this relationship poses a challenge.


In the present article, Drs. Benedictus and her colleagues evaluate the association and potential risk factors for cognitive decline after intracerebral hemorrhage (ICH). Although ICH accounts for only 10% of all strokes, the mortality rate is over 50% within the first year. Although various scores have been created to help predict which patients will survive and regain functional independence (ICH score and FUNC score), there has been a paucity of data on cognitive outcomes after ICH. 

In order to assess risk factors for cognitive decline after ICH, the authors evaluated a cohort of adult patients with ICH. MRI was used to evaluate for cortical atrophy, white matter hyperintensities, lacunes, and microbleeds. Patients were prospectively followed for cognitive decline using MMSEs at 6 months, 12 months, and then annually after ICH.

Out of a cohort of 560 patients, 167 were included in the final analysis. During a median follow-up of 4 years, 37% of patients developed cognitive decline. Perhaps not surprisingly, pre-existing cognitive impairment was the strongest predictor of cognitive decline after ICH. In addition, both previous stroke/TIA and severity of cortical atrophy (but not presence of white matter hyperintensities, microbleeds, or lacunes) were associated with cognitive decline after ICH. In a post-hoc sensitivity analysis evaluating risk factors of cognitive decline in patients without pre-existing cognitive decline, only severity of cortical atrophy remained associated with development of cognitive decline. Finally, ICH location (lobar or non-lobar) was not associated with development of cognitive decline.

Limitations include: 1) baseline demographics (age) and radiographic risk factors such as cortical atrophy were not equally distributed between patients who had cognitive data available for analysis; 2) cognitive decline was solely based on MMSE which made it impossible to perform in patients with certain neurological sequelae of stroke such as aphasia; and 3) cognitive status was only evaluated in patients who survived for at least 1 year after ICH (since patients needed 2 MMSE performed 6 months apart), which limits generalizability of this study.

Overall, what does this study tell us? First, more than 1/3 of patients with ICH will develop cognitive decline. Second, risk factors for the development of cognitive decline after ICH are already present before ICH occurs – baseline cognitive impairment, prior stroke/TIA, and baseline cortical atrophy. Third, the interaction between neurodegenerative and vascular pathology is complex, but this study emphasizes the need for better stroke prevention, which, in turn, may lead to decreased neurodegeneration and perhaps vice versa.

By |September 23rd, 2015|hemorrhage|1 Comment

Readmission rates and mechanical ventilation in stroke

 
Stroke is a major cause of disability, with previously published studies demonstrating that 12% of stroke patients are mechanically ventilated with 16% of these subsequently undergo tracheostomy. Readmission rates in mechanically ventilated patients are a marker of morbidity and health care cost, which has been evaluated in medically and surgically ill patients, but not previously in stroke patients; here, the authors looked at readmission rates for patients who received mechanical ventilation, stratified by whether tracheostomy was performed.



One-quarter of stroke patients who underwent mechanical ventilation underwent placement of a tracheostomy prior to discharge; a small minority of those who were discharged without a tracheostomy did ultimately go on to receive a tracheostomy on a subsequent readmission. Even after adjusting for stroke type, comorbidities, vascular risk factors, and demographic characteristics, 30-day readmission rates were found to be higher in patients who underwent tracheostomy compared to those who did not, with sepsis being the most common diagnosis at time of readmission, followed by pneumonia, congestive heart failure and device related complication.

What does this mean for clinicians? Although tracheostomy does seem to be associated with higher readmission rates in stroke patents, the readmission rate is similar to that seen in patients hospitalized for medical illnesses such as pneumonia and that seen in general intensive care unit patients. One interpretation of the data, which the authors opined, is that tracheostomy placement in a stroke patient does not necessarily imply drastically worse outcomes, given that the readmission rate is similar in other medically ill populations. Some confounding factors, such as differences in stroke severity, was not available to the authors for analysis, which could potentially impact which patients require tracheostomy and be a similar independent factor in which patients require readmission. Results from this study therefore do not provide definitive guidance on how to necessarily counsel patients and their families on the long-term outcomes of mechanical ventilation and tracheostomy in stroke patients, but may help clinicians place the consequences of tracheostomy in this specific population into a larger context and perspective.

By |September 22nd, 2015|treatment|0 Comments

What the FAST-MAG Study teaches us about EMS Systems of Care for Acute Stroke

Danny R. Rose, Jr., MD 

Sanossian N, Liebeskind DS, Eckstein M, Starkman S, Stratton S, Pratt FD, et al. Routing Ambulances to Designated Centers Increases Access to Stroke Center Care and Enrollment in Prehospital Research. Stroke. 2015

Patients with acute stroke have better outcomes when treated at organized stroke centers. Emergency Medical Services (EMS) providers play a critical role in the stroke care system by identifying patients with suspected stroke and then providing rapid transport to a facility providing an appropriate level of specialty care. Since 2007, this notion has been reflected in the American Stroke Association guidelines, which recommend Emergency Medical Services (EMS) systems preferentially route acute stroke patients to certified stroke centers that have proven their capability to deliver stroke care. Although this was supported by legislation or regulations in states and counties covering 53% of the US population by 2010, few studies have investigated whether these policies increase access to stroke center care. The impact on research associated with having a greater proportion of acute stroke patients treated at stroke centers, many of which actively enroll patients in clinical trials, is unknown.

Although the FAST-MAG study, a phase 3 clinical trial for prehospital initiation of magnesium vs. placebo for suspected acute stroke patients, failed to show a statistically significant benefit, it proved the feasibility of conducting a trial utilizing prehospital EMS protocols in a large metropolitan area spanning multiple provider agencies. What makes this study unique was that it was carried out in Los Angeles County over a period that in which there was a substantial change in the way EMS routed patients due to the implementation of a regional system of stroke care. Sanossian et al. performed an analysis using data from this study to investigate how the implementation of preferential routing for acute stroke patients impacted Emergency Department arrival times, the percentage of patients treated at an acute stroke center, and the numbers of patients enrolled in this prehospital stroke study. 
 

A total of 1627 subjects were enrolled in Los Angeles County over the course of the study, with 863 (53%) prior to and 764 (47%) after adoption of the countywide EMS routing protocol. In the nearly 5 years prior to EMS routing, only 90/863 (10%) of patients were transported to a designated Primary Stroke Center (PSC). EMS routing increased this proportion dramatically, with 698/764 (91%) of patients enrolled after the protocol implementation (P<0.001). Interestingly, the time from EMS arrival on scene to ED arrival actually decreased slightly after the routing change (34.5 min. vs 33.5, p=0.045). An analysis focused on the years immediately before and after the stroke center diversion policy was implemented showed an equally impressive improvement in the percentage of patients transported to PSCs (17% vs. 88%, P<0.0001), shorter scene to door times (33.6 min. vs 34.5, p=0.221), and a greater mean monthly enrollment into the FAST-MAG study (21.2 vs 17.9 subjects per month)

The analysis illustrates the dramatic effect that a properly implemented policy can have on improving the proportion of suspected acute stroke patients treated at stroke centers without detrimentally affecting transport times, one of the most common concerns regarding these types of changes. As these and similar changes designed to ensure acute stroke patients are preferentially treated at Joint Commission-certified stroke centers are implemented, there will likely be benefits beyond the more efficient conduct of clinical trials.

There, however, are significant limitations to the study that affect its generalizability. As in most major metropolitan areas in the US, Los Angeles County has a large amount of adult ED receiving facilities in a relatively small geographic area, with a total of 69 facilities participating in this study. The proportion of these facilities that obtained PSC certification increased steadily throughout the course of the trial, from 9 at the initiation of the routing policy in 2009 to a total of 29 by the trial end in December 2012. Although this can serve as a useful model for other major metropolitan areas in the US, access to primary stroke centers is more limited in large portions of the country. In these areas, routing suspected stroke patients exclusively to stroke centers could result in important delays in evaluation and treatment. This should not discourage policymakers in rural areas from adopting protocols to ensure acute stroke patients are triaged and transported efficiently. In these relatively underserved areas, collaboration and cooperation between stroke centers and critical access hospitals will likely remain a crucial component of stroke systems of care as medical infrastructure continues to evolve and mature.

On developing multi-national acute stroke care quality measures

Neal S. Parikh, MD   

Norrving B, Bray BD, Asplund K, Heuschmann P, Langhorne P, Rudd AG, et al. Cross-National Key Performance Measures of the Quality of Acute Stroke Care in Western Europe. Stroke. 2015 

In this issue of Stroke, representatives from the European Implementation Score Collaboration describe the process and results of an effort to establish common acute stroke care quality measures.

In order to compare quality measures across nations and regions in Western Europe, the collaborators convened to establish agreed-upon metrics. Physician and patient representatives from multiple Western European nations met to establish two tiers of indicators: Tier I – essential, Tier 2 – desirable. The European Stroke Organization endorsed the final measures.

Table 2 summarizes the 30 performance measures of acute stroke care formulated by this group. There are a number of limitations. The measures include basic patient characteristics, but not patients’ basic vascular risk factors, the omission of which limits the ability to make adjusted comparisons across nations. Additionally, while the measures are grossly in concordance with current evidence, they are non-specific. For example, the duration of cardiac arrhythmia detection and the nature of anti-platelet therapy (mono or dual) are not specified. Finally, the outcome measures are rudimentary: 90 day mortality and modified Rankin Scale. These limitations are anticipated given the variability in resources across nations. The authors also admit that the guidelines cannot keep up with research; for example, provision of endovascular therapy is not included in their quality measures.

Given rapidly mounting evidence regarding high-impact stroke treatment and secondary prevention interventions, it is necessary to document acute stroke management quality measures to ultimately facilitate higher levels of evidence-based stroke care. Efforts such as these are important as quality measures may reveal disparities and thereby inform the decisions of policy-makers and funding organizations. Additionally, these quality measures may serve as a model for other nations.

Aggressive Medical Therapy is the Key!!!

Russell Mitesh Cerejo, MD 

Chaturvedi S, Turan TN, Lynn MJ, Derdeyn CP, Fiorella D, Janis LS, et al. Do Patient Characteristics Explain the Differences in Outcome Between Medically Treated Patients in SAMMPRIS and WASID? Stroke. 2015 

Dr. Chaturvedi and colleagues have put to rest the question of whether patient characteristics in the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) and Warfarin Aspirin Symptomatic Intracranial Disease (WASID) trials differed given the low incidence of primary outcomes in the SAMMPRIS group. 


In their paper, “Do patient characteristics explain the differences in outcome between medically treated patients in SAMMPRIS and WASID?” they compared patients from WASID trial with identical inclusion criteria as that of SAMMPRIS to establish that it was truly aggressive medical therapy that was responsible for the lower incidence rated of primary outcomes. The 1, 2 and 3-year rates of the primary endpoint were 42%, 41% and 48% lower respectively in SAMMPRIS medically-treated patients compared with WASID patients who met the SAMMPRIS inclusion criteria. This was despite the fact that patients enrolled in SAMMPRIS had higher percentage of hypertension, severe stenosis, elevated body mass index and higher rate of old infarcts in the symptomatic artery territory. SAMMPRIS patients had a better lipid profile, likely related to the statin therapy in the trial. The baseline characteristics that were both different between the studies and related to outcome and thus potential confounders were no statin use at enrollment (more prevalent among WASID patients) and old infarcts in the territory of the symptomatic artery (more prevalent among SAMMPRIS patients). After adjusting for this, the estimated hazard ratio for WASID vs SAMMPRIS was 1.9 (95% CI = 1.1 – 3.2, p = 0.016) demonstrating a higher risk of the outcome among WASID patients. This study elucidates the likely reason for improved outcomes seen in the medical arm of SAMMPRIS compared to the predicted rates based on the WASID trial.

By |September 17th, 2015|treatment|1 Comment