American Heart Association

Hope for the Brokenhearted

Rachel Forman, MD

Siedler G, Sommer K, Macha K, Marsch A, Breuer L, Stoll S, et al. Heart Failure in Ischemic Stroke: Relevance for Acute Care and Outcome. Stroke. 2019.

The topic of heart failure (HF) is not uncommon in the stroke world. It is a known risk factor for stroke and is related to prothrombotic/proinflammatory states, worsening of cerebral tissue oxygenation, and hemodynamic impairment. There is also consideration if HF may affect the safety and efficacy of acute stroke therapies. Some concerns include reduced circulation after tPA with low cardiac output or difficulties with anesthesia management during MT. This study by Siedler et al. aimed to look at the effects of HF on stroke patients who received tPA, mechanical thrombectomy (MT), or both. The authors note the importance of this study and that many of the prospective clinical trials have excluded HF patients.

Patients who received tPA or MT at a university stroke center were included into a prospective registry. Patients with HF were identified based on their echocardiograms (transthoracic or transesophageal) done as a part of the stroke evaluation. The impairment of left ventricular ejection fraction (LVEF) was categorized as mild if >35% EF, moderate if 25-35% EF, and severe if <25% EF. Functional outcome was assessed after 90 days by telephone interviews and favorable outcome was considered mRS 0-2.  

Article Commentary: “Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis”

Wayneho Kam, MD

Wu C, Sun C, Wang L, Lian Y, Xie N, Huang S, et al. Low-Dose Tirofiban Treatment Improves Neurological Deterioration Outcome After Intravenous Thrombolysis. Stroke. 2019.

The current standard of practice is to avoid the use of antithrombotic agents within the first 24 hours after receiving intravenous thrombolytics. This is due to concern that the concurrent use of antiplatelets or anticoagulants with recent thrombolytic administration may increase the risk for bleeding events. The concern may be unfounded, however, particularly given the relatively short half-life of alteplase.

There are instances, of course, when use of such medications within 24 hours of alteplase administration may be warranted, such as with concomitant endovascular therapy with stent placement or acute myocardial infarction.

What if early neurological deterioration occurs in patients after they received tPA, in the absence of a clear explanation, such as hemorrhagic conversion or cerebral edema? Will these patients benefit from early initiation of antiplatelet therapy?

Investigating the Causes of Declining Carotid Endarterectomies

Raffaele Ornello, MD

Johal AS, Loftus IM, Boyle JR, Naylor AR, Waton S, Heikkila K, et al. Changing Patterns of Carotid Endarterectomy Between 2011 and 2017 in England: A Population-Based Cohort Study. Stroke. 2019;50:2461–2468.

Carotid endarterectomy (CEA) is effective for secondary stroke prevention in symptomatic patients, while its effectiveness in asymptomatic patients is a matter of debate. Data suggest that CEAs are declining worldwide; however, the reasons for that decline are unclear.

To investigate those possible causes, the authors reviewed data from the English National Vascular Registry in the 2011-2017 period and confirmed a decline of CEAs in both symptomatic and asymptomatic patients. In detail, CEAs performed in asymptomatic patients declined by 63%, from 722 in 2011 to 265 in 2017, while those performed in symptomatic patients declined by 25%, from 4992 in 2011 to 3482 in 2017.

Article Commentary: “Cannabis and Cannabinoid Biology in Stroke”

Pamela Cheng, DO

Choi S-H, Mou Y, Silva AC. Cannabis and Cannabinoid Biology in Stroke: Controversies, Risks, and Promises. Stroke. 2019;50:2640–2645.

Stroke remains one of the leading causes of death and disability in the United States. Currently, the main therapeutic approach includes thrombolysis and mechanical thrombectomy. However, immediate reperfusion therapy does not tell the whole story. Following a stroke, there are complex biochemical events that occur that lead to excitotoxicity and oxidative stress, which may contribute to long-term functional outcomes. As such, there has been great interest and research in the field of neuroprotection. While there are currently no approved neuroprotective treatment options for stroke, there have been some promising yet conflicting results on the endocannabinoid system (ECS).

The ECS is composed of endogenous, lipid-based neurotransmitters that bind to the cannabinoid receptors. The ECS has shown promise in a wide range of pathological conditions and neurological disorders. In stroke, there is evidence that the ECS is altered in both animals and humans, and may contribute to the consequences of ischemic stroke. While studies have been conflicting in either supporting or refuting the use of cannabinoids, they remain a prominent research focus.

Antiplatelet Therapy and Functional Outcomes After ICH

Lina Palaiodimou, MD

Murthy SB, Biffi A, Falcone GJ, Sansing LH, Torres Lopez V, Navi BB, et al. Antiplatelet Therapy After Spontaneous Intracerebral Hemorrhage and Functional Outcomes. Stroke. 2019

Initiation of antithrombotic therapy (antiplatelet or anticoagulant) after intracerebral hemorrhage (ICH) has long been a matter of conflict among clinicians dealing with stroke patients. Given that the treatment of ICH in the acute phase is mostly supportive, one can understand the anxiety of the clinicians who want to prevent an ICH recurrence. However, according to American Heart Association/American Stroke Association (AHA/ASA) guidelines, the recommendation that “anticoagulation after nonlobar ICH and antiplatelet monotherapy after any ICH might be considered, particularly when there are strong indications for these agents” is not well established (Class IIb) and is based on evidence derived from nonrandomized studies (Level of Evidence B). That is why studies aiming to shed light on this matter are more than welcome from the scientific community of stroke.

The study by Murthy et al. is an attempt to enrich the scarce data regarding the impact of antiplatelet therapy (APT) initiation after ICH on functional outcomes. For that reason, the authors separately analyzed data from 3 large cohort studies [ICH study at Massachusetts General Hospital (MGH), Virtual International Stroke Trials Archive-ICH (VISTA-ICH), ICH database of Yale University School of Medicine], consisting of 1801 ICH patients in total. Inclusion criteria were: diagnosis of primary ICH in CT-scan, age >18 years, and complete follow up at 90 days. Exclusion criteria were: previous history of ICH, secondary cause of ICH, and prior use of anticoagulants.

Stroke Secondary to Atherosclerotic Aortic Arch Plaques: A Reminder

Victor J. Del Brutto, MD

Ntaios G, Pearce LA, Meseguer E, Endres M, Amarenco P, Ozturk S, et al. Aortic Arch Atherosclerosis in Patients With Embolic Stroke of Undetermined Source: An Exploratory Analysis of the NAVIGATE ESUS Trial. Stroke. 2019

When it comes to establishing the mechanism of injury in a stroke victim, the label “unknown/undetermined” deprives the patient of receiving the appropriate prognosis and strategy for secondary prevention. One-fourth of ischemic strokes are identified as cryptogenic without a definite understanding of the cause, and a sizable proportion of them will fit into the concept of embolic stroke of undetermined source (ESUS). The cause of ESUS could be an under-recognized cardiac source or a non-stenosing arterial lesion. Despite seminal studies in the 1990s that have identified a causal association between protruding plaques in the aortic arch and ischemic stroke, aortic arch atherosclerosis (AAA) is often overlooked during routine stroke work-up, thus falling into the category of stroke of undetermined etiology.

The current manuscript published by Ntaios and colleagues reports the exploratory analysis of the subgroup of individuals who participated in the New Approach Rivaroxaban Inhibition of Factor Xa in a Global Trial Versus ASA to Prevent Embolism in Embolic Stroke of Undetermined Source (NAVIGATE-ESUS) trial and underwent transesophageal echocardiogram (TEE) for evaluation of AAA. The authors found a prevalence of 19% of AAA among patients with ESUS, from which one-third (8% of the total cohort) were considered to have high-risk complex plaques as defined by the presence of ulceration, thickness greater than 4 mm, or presence of a mobile thrombus. As noticed by the authors, the prevalence of AAA might be underestimated due to lower atherosclerotic risk factors in those who underwent TEE. Increasing age, diabetes mellitus and aortic valve disease, as well as geographic region (east Asia and eastern Europe), were significant determinants of AAA in the multivariable analysis. In addition, chronic infarcts and multi-territorial infarcts were associated with AAA, arguing against the common belief that multifocal strokes are exclusively cardioembolic. There was a non-significant trend for higher rate of stroke recurrence in patients with complex AAA (7.2% annualized rate) when compared to those without AAA (5.6% annualized rate). Data from this analysis was merged with two other randomized controlled trials to construct a meta-analysis of anticoagulation versus antiplatelet therapy in patients with cryptogenic stroke and AAA. The meta-analysis found no significant difference in the rate of stroke recurrence between the two antithrombotic approaches.

ESUS Subpopulation with Carotid Atherosclerosis: Do the Overall Results Differ?

Piyush Ojha, MBBS, MD, DM

Ntaios G, Swaminathan B, Berkowitz SD, Gagliardi RJ, Lang W, Siegler JE, et al. Efficacy and Safety of Rivaroxaban Versus Aspirin in Embolic Stroke of Undetermined Source and Carotid Atherosclerosis. Stroke. 2019;50:2477–2485.

Embolic stroke of undetermined source (ESUS), accounting for approximately 20% of all ischemic strokes, has been a hotly debated topic in the stroke community. The term encompasses cryptogenic strokes believed to be embolic in origin, which are not lacunar and without a cardiac or proximal large artery source. Patients qualifying as ESUS show a lot of pathophysiological heterogeneity, reflecting in the lack of sufficient evidence of trend towards a particular class of drugs and hence difficult to formulate a pharmacological plan. Multiple possible sources of emboli in these patients may explain the non-uniform response to anticoagulation over antiplatelets.

Several studies (including two major trials, NAVIGATE ESUS and RE-SPECT ESUS) have compared direct oral anticoagulants and aspirin in patients with recent ESUS for secondary stroke prevention, and failed to show any benefit of anticoagulation over antiplatelets, with associated higher risk of bleeding.

Poststroke Hypertension: Beneficial or Harmful?

Melissa Trotman-Lucas, PhD, BSc
@TroLucaM

Thakkar P, McGregor A, Barber PA, Paton JFR, Barrett C, McBryde F. Hypertensive Response to Ischemic Stroke in the Normotensive Wistar Rat: Mechanisms and Therapeutic Relevance. Stroke. 2019;50:2522-2530.

Sudden increased blood pressure (BP), known as hypertension, following an ischaemic insult is the scenario for ~80% of acute ischaemic stroke (AIS) patients. This poststroke hypertension is the subject of continued scientific debate, with both the mechanism and its therapeutic relevance still poorly understood. There are two potential sides to the role of poststroke hypertension in AIS tissue damage: exacerbation and protection. Exacerbation of damage to vulnerable ischemic tissue may occur alongside promotion of edema formation; moreover, this abrupt increase in BP can increase the risk of cardiovascular events, including further strokes and heart attacks. On the flip side, this increased BP may be a reaction by the body to increase blood supply to the brain tissue, increasing oxygenation of the penumbral tissue. Therefore, creating the conundrum that treatment to reduce BP levels in AIS may be protective but, on the other hand, it may also escalate tissue damage and increase the risk of a poorer patient outcome.

A recent study by Thakkar et al., published in Stroke, sought to answer whether a neurally mediated increase in systemic BP protects cerebral perfusion by opposing the increase in intracranial pressure (ICP) through increasing supply pressure to the tissues. Undertaking this by characterising the cerebrovascular, ICP and cerebral oxygenation responses in a rat AIS model. Testing also the physiological impact of hypertension prevention on the maintenance of oxygenation in the penumbra and on functional recovery poststroke.

RE-SPECT Dabigatran in ESUS?

Grace Y. Kuo, MD, MS, BA

Diener H-C, Sacco RL, Easton JD, Granger CB, Bernstein RA, Uchiyama S, et al. Dabigatran for Prevention of Stroke after Embolic Stroke of Undetermined Source. N Engl J Med. 2019; 380:1906-1917.

In the age of novel oral anti-coagulants (NOACs), secondary stroke prevention is arriving at a crossroads of innovation versus tradition. Many cryptogenic strokes, which make up 20-30% of ischemic strokes, are suspected to be embolic strokes of undetermined source (ESUS). In this population, do NOACs have a role in secondary stroke prevention?

Sponsored by Boehringer Ingelheim, the RE-SPECT ESUS study investigated the efficacy of dabigatran in preventing recurrent strokes in an international multi-center, randomized, double-blind, parallel group trial against aspirin. 5390 patients from 564 sites were randomly assigned to either dabigatran or aspirin, and followed for average of 19 months (6-36 months) for the primary outcome of recurrent strokes. ESUS was defined as a non-lacunar ischemic stroke in a patient with no extracranial or intracranial atherosclerosis causing 50% or greater stenosis in arteries supplying the area of the stroke, no A-fib greater than 6 minutes, and no intra-cardiac thrombus. Study subjects received 2 pills – either dabigatran and an aspirin placebo, or a dabigatran placebo and aspirin. In patients older than 75 years old or with impaired renal function, an adjusted dose of dabigatran was given. Primary efficacy outcome was recurrent ischemic, hemorrhagic or unspecified type stroke, assessed in a time-to-event analysis.

By |October 2nd, 2019|clinical|0 Comments

Sex Differences in Outcome After Endovascular Therapy

Kristina Shkirkova, BSc
@KShkirkova

Sheth SA, Lee S, Warach SJ, Gralla J, Jahan R, Goyal M, et al. Sex Differences in Outcome After Endovascular Stroke Therapy for Acute Ischemic Stroke. Stroke. 2019;50:2420-2427.

A recent publication by Sheth and colleagues examined the effect of sex on outcomes after endovascular stroke thrombectomy in acute ischemic stroke.

The study analyzed a pooled cohort of patients enrolled in the SWIFT (Solitaire FR With the Intention for Thrombectomy), STAR (Solitaire FR Thrombectomy for Acute Revascularization), and SWIFT PRIME (Solitaire FR With the Intention for Thrombectomy as Primary Endovascular Treatment) Phase-III clinical trials. The study included a total of 389 patients treated with Solitaire stent retriever within 8 hours of stroke onset, who presented with occlusion of proximal cerebral arteries and moderate to severe neurological deficits. Patients with uncontrolled hypertension, sensitivity to contrast agents, and intracranial hemorrhage or major ischemic change in more than a third of the middle cerebral artery territory were excluded from the study. 

By |October 1st, 2019|clinical|0 Comments