American Heart Association

Conference

World Stroke Congress: RAISE Session on New Frontiers in Neurocardiology in the 2020s

Sishir Mannava, MD
@sishmannmd

World Stroke Congress
October 28–29, 2021

Neurocardiology: The Neurologist’s Perspective – Dr. Edip Gurol

Dr. Gurol started by discussing the importance of the neurologist classifying stroke etiologies, and ultimately concern for cardioembolic infarct, and the importance of long-term cardiac monitoring in these patients as highlighted by the findings in the CRYSTAL-AF and REVEAL-AF studies. Another important role of neurologists in these patients is stratifying ICH risk if they require anticoagulation (AC). The FDA approved AC for stroke prevention, include warfarin, direct oral antiocoagulants (DOACs), and left atrial appendage closure (LAAC) with WATCHMAN/Amulet devices. Importantly, AC increased intracranial hemorrhage (ICH) risks, and outcomes of AC-associated ICH are extremely poor. High-risk categories include prior brain bleed (of many types), brain microbleeds on MRI (as highlighted in the CROMIS-2 study), white matter disease on MRI, and cognitive/gait problems. AC has been associated with between 5-7x the risk of ICH as compared to antiplatelets (AP). In a recent trial from the UK, which randomized patients to AC vs AP after spontaneous ICH, 8% (AC) as opposed to 4% (AP) had recurrent ICH. Mortality of AC-related ICH is very high, ~50%. Having a prior history of ICH related to hypertension < mixed-ICH < cerebral amyloid angiopathy ICH significantly increases recurrent ICH risk as well. This concept also applies to patients who have independent evidence of lobar microbleeds. Interestingly, Dr. Gurol highlighted a 2019 study from Neurology that showed moderate/severe white matter hyperintensities were associated with ~6% increased risk of ICH if given AC (Marti-Fabregas et al). Regarding LAAC in nonvalvular atrial fibrillation, the PRAGUE-17 trial showed that stroke prevention and bleeding risks were similar when comparing closure to DOACs. Dr. Gurol closed with discussion of patent foramen ovale (PFO) closure for stroke prevention, highlighting that hypercoagulable states and other causes should be evaluated prior to PFO closure. Ultimately, all decision-making regarding AC or device placement (LAAC, PFO) should be shared with the patient.

AHA Scientific Sessions: “Updates in Stroke: Careers & Future Directions in Vascular Neurology”

Meghana Srinivas, MD

AHA Scientific Sessions 2021
November 13–15, 2021

Session: “Updates in Stroke: Careers & Future Directions in Vascular Neurology”
Panelists:
Drs. Anjail Sharrief, Ashutosh Jadhav, Louise McCullough, Alicia Zhao

This session kickstarted by highlighting the timeline to consider a career path as a neurology trainee and why it is important to do a fellowship. In current times, there is rapid growth in the field of medicine, and with this, there is an increased demand to have specialists, and hence choosing a fellowship is important. The panelists discussed extensively a career in vascular neurology and why we need more vascular neurologists in practice. There was a shocking revelation showing the dearth of vascular neurologists as compared to our counterparts, cardiologists. The ratio of graduating stroke neurologists to that of cardiologists is ~1:10; however, the disease burden is not proportionate. Why is this? A part of this could be attributed to the amount of exposure we get in acute stroke management during our training as residents, making us comfortable to manage these patients and hence inclined towards either an inpatient or outpatient setting without a formal fellowship. But wait, there is more to it: The panelists gave us an insight into poststroke care and management, which is also equally important. They discussed in detail patient care both in acute and in the post-discharge period, emphasizing that a fellowship is important, as it gives you an opportunity for continuity of care even at the community level.

CHIP and Stroke: Risk for Cerebrovascular Diseases Dwells in the Bone Marrow

Aurora Semerano, MD
@semerano_aurora

Bhattacharya R, Zekavat SM, Haessler J, Fornage M, Raffield L, Uddin MM, Bick AG, Niroula A, Yu B, Gibson C, et al. Clonal Hematopoiesis Is Associated With Higher Risk of Stroke. Stroke. 2021.

Clonal hematopoiesis of indeterminate potential (CHIP) consists of a clonal expansion of circulating blood cells that arises from somatic mutations in hematopoietic stem cells. This condition usually does not entail abnormal blood cell counts and is common in older individuals, since it has been detected by DNA sequencing in >10% of people aged 70+ years. While carrying a relatively modest risk of developing hematological malignancy, from 2014 onwards CHIP has been unexpectedly and increasingly recognized as an independent, non-traditional risk factor for cardiovascular diseases and atherosclerosis, underlying the important interplay between aging, inflammation, and cardiovascular health. Interestingly, CHIP is determined by mutations in a handful of genes, which are currently under active investigations in experimental models. For example, accelerated atherosclerosis and increased release of inflammatory cytokines have been found in mice that bear TET2-deficient leukocytes. The relationship between CHIP and stroke risk was first reported in 2014 by Jaiswal et al.1 Indeed, by analyzing two cohorts of ~3000 patients, the presence of a somatic mutation was associated with an increased risk of ischemic stroke with a hazard ratio of 2.6 (95% CI, 1.4 to 4.8).

In the article by Bhattacharya et al. recently published in Stroke, the authors aimed at expanding the knowledge about the association between CHIP and risk of cerebrovascular events, taking into account both ischemic and hemorrhagic strokes, as well as stroke etiology. A total of 86,178 individuals from 8 prospective cohorts or biobanks were included. The overall prevalence of CHIP at baseline was 6%. CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14; 95% CI, 1.03–1.27). Unexpectedly, this relationship was primarily driven by a 24% increased odds of hemorrhagic stroke, particularly subarachnoid hemorrhage. Though CHIP was not found to be associated with ischemic stroke overall, in exploratory analyses from one female patient cohort, CHIP was more strongly associated with small vessel disease than with large artery atherosclerosis or cardioembolic etiologies. When analyzing mutations in specific CHIP genes, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke.

World Stroke Congress: “Stroke in Low to Middle Income Countries”

Ericka Samantha Teleg, MD

World Stroke Congress
October 28–29, 2021

Plenary Session: “Stroke in Low to Middle Income Countries”

While the landscape of stroke changes in terms of innovations, pathways and technology, there is a continuing increase of stroke burden in the low to middle income countries (LMICs). This session was moderated by Dr. Norlinah Ibrahim and Dr. Mayowa Owolabi.

Dr. Owolabi opened the discussion by giving an overview of the Lancet Commission in giving evidence-based recommendations that are pragmatic in nature extending to primary, secondary, and tertiary prevention, keeping in mind that these regions bear a burden due to limited resources. He emphasized the Stroke Quadrangle that includes epidemiological surveillance, acute care, rehabilitation, palliative care, health promotion, and disease prevention. He set the stage by reiterating that there is scarcity of funding for primary stroke prevention, particularly in LMICs. There is indeed an absence of an integrative approach. Regional and national differences in policymaking are also a variable. 

ESOC 2021: Challenging Clinical Situations in Stroke Medicine (and Tips to Face Them)

Aurora Semerano, MD
@semerano_aurora

European Stroke Organisation Conference
September 1–3, 2021

Session: “Acute Stroke Treatment in Difficult Clinical Situations: In-Hospital Strokes and Other Challenges,” September 2, 2021

Making decisions in stroke medicine is a difficult task and may turn to be really challenging in selected cases, which, however, are quite frequent in our clinical practice. These daily challenges were the focus of the discussion in the session chaired by Daniel Strbian (Finland) and Silke Walter (Germany). Also, some useful tips for more confident decisions were proposed.

When deciding about thrombolysis in patients with recent surgery, existing studies are mostly retrospective and heterogenous, thus evidence for the best practice is very low. Gordian J. Hubert (Germany) suggested a comprehensive approach, which includes the evaluation of the risk of bleeding in the surgical wound (in terms of size, time from surgery, vascularization of the tissue), the damage of a potential bleeding in that site, and the possibility of measures to efficiently stop the bleeding (i.e., compressibility, surgical intervention). Similarly, in patients with recent trauma, the evaluation of the bleeding risk at the trauma site can be crucial, whereas estimating the damage of a potential bleeding may be challenging since location of trauma is often unknown.

ESOC 2021: Thrombosis and Inflammation Team Up in Ischemic Stroke

Aurora Semerano, MD
@semerano_aurora

European Stroke Organisation Conference
September 1–3, 2021

Session: “Inflammation, Thrombosis and Stroke Pathogenesis,” September 3, 2021

The complex interplay between inflammation and thrombosis in ischemic stroke was the subject of the interesting scientific session chaired by Mervyn D. Vergouwen (Netherlands) and Christoph Kleinschnitz (Germany). The five speakers dissected the topic by presenting the main players involved in pathophysiology of stroke-related thrombo-inflammation, and prospected potential interventions of immune modulation.

Bernhard Nieswandt (Germany) showed how platelets, besides their well-established functions, have a critical role in inflammation. They are involved not only in the process of thrombus formation, but also in the subsequent mechanisms of infarct growth. Identifying the optimal target to interfere with platelet activity is crucial, due to the possible risk of hemorrhagic transformation. Two promising axes are discussed, namely the immunomodulatory function of von Willebrand Factor through its receptor on platelets Glycoprotein Ib, and the interplay with the kallikrein system and Factor XII activation. The resulting infiltration of immune cells (including T cells) into the ischemic brain contributes to the damage. Importantly, he pointed out that thrombo-inflammation doesn’t start after recanalization, but it is still ongoing during the occlusion, sustained by the collateral blood flow. This is supported in humans by a recent elegant work,1 which reported for the first time that leukocytes strongly accumulate in cerebral vessels distal to the occlusion. Bearing this in mind is fundamental to designing the optimal treatment.

ESOC 2021 Session: “Non-Reperfusion Therapies for Acute Ischemic Stroke Treatment: Something New in the Pipeline?”

Karissa Arthur, MD

European Stroke Organisation Conference
September 1–3, 2021

Dual Antiplatelet Therapy for Minor Acute Ischemic Stroke: Clopidogrel vs Ticagrelor: Pierre Amarenco, Paris University

In this session, Dr. Amarenco compared clopidogrel versus ticagrelor for minor acute ischemic stroke. He first summarized data for aspirin monotherapy showing that it reduces the risk of ischemic stroke by 60%, and the 6-week risk of disabling stroke by 70%. He then called to attention the CHANCE and POINT trials, as well as a pooled analysis of both, showing that dual antiplatelet therapy with aspirin plus clopidogrel after a minor stroke or TIA is 34% superior to aspirin alone in preventing stroke in the first 21 days. Dr. Amarenco went on to discuss the shortcomings of clopidogrel, with specific regard to CYP2C19 loss of function carriers in which there is less efficacy for stroke prevention. In contrast to clopidogrel, ticagrelor is a direct acting drug which does not require biotransformation, binds reversibly to platelets, has faster onset, higher platelet inhibition, and faster offset and therefore has a more attractive profile than clopidogrel. 

ESOC 2021 Session: “Targeting Cardiac Disease in Stroke Prevention: Joint Session With the European Society of Cardiology (ESC)”

Thomas Meinel, MD
@TotoMynell

European Stroke Organisation Conference
September 1–3, 2021

Stroke prevention — especially in patients with atrial fibrillation — is a team effort of cardiologists and vascular neurologists. Vice-versa, work-up of cardiac disease and cardioaortic sources of embolism is a joint effort of stroke physicians and cardiologists. Several novel diagnostic options, medical therapies and devices are available in the cardiovascular field. Hence, this joint session of the ESO and ESC was a logical consequence of intensified collaboration of these two big societies.

The first speaker was Marta Rubiera from Spain, who elaborated on the diagnostic options to identify structural cardioaortic sources of embolism in stroke patients. Presenting the expected diagnostic findings and weighing nicely the pros and cons of each modality, she guided the audience to choose the correct test according to the patient and the stroke characteristics. Cardiac MRI and cardiac CT represent novel diagnostic options in selected patients, but echocardiography remains the working horse of stroke work-up. However, the lack of randomized diagnostic studies with clinical outcomes and the uncertainty of what to do with minor sources of embolism remain a major drawback of this daily task during stroke unit rounds. Joint efforts of cardiology and neurology are necessary to overcome this evidence gap.

ESOC 2021 Session: “Large Artery Stroke: Carotid Disease, Plaque and Beyond”

Karissa Arthur, MD

European Stroke Organisation Conference
September 1–3, 2021

Cervical Artery Dissection: Christopher Traenka, University Hospital Basel

Dr. Traenka discussed carotid artery dissection (CeAD) in this talk. He first discussed CeAD and sports. Patients with CeAD obtained during stroke should refrain from any sports activities for at least one month, and this period may need to be prolonged considering the patient’s clinical course. When resuming activities, patients should start at low intensity and gradually increase activity. Most patients will go back to full activity in 6-12 months.

ESOC 2021 Session: “Closing Ceremony and Large Clinical Trials 2”

Vignan Yogendrakumar, MD, MSc
@VYogendrakumar

European Stroke Organisation Conference
September 1–3, 2021

Wrapping up our coverage of this year’s ESOC, the second round of results from major clinical trials!

APACHE-AF: Apixaban after Anticoagulation-Associated Intracerebral Hemorrhage In Patients with Atrial Fibrillation: A Randomized, Open-Label, Phase 2 Trial

APACHE-AF was a prospective, randomized, open-label clinical trial, recruiting adults with a history of atrial fibrillation and anticoagulation associated ICH. Following their ICH event (days 7-90 days post ICH event), participants were randomized to apixaban 5mg twice daily or to avoiding anticoagulation. Primary outcome was vascular death or non-fatal stroke and was evaluated using a Cox proportional hazards regression model. Between January 16, 2015 and July 6, 2020, 101 participants (46% female, median age 77 years) were recruited at a median of 46 (IQR 21-74) days after ICH in an intention to treat analysis. Participants were followed for a median of 1.9 (IQR 1.0-3.1) years. There were 10 patients who crossed over. For the primary outcome, comparing Apixaban to Avoiding Anticoagulation: Adjusted HR: 1.05 (0.48-2.31), indicating no major difference between the two groups. There were no major differences in subsequent ICH between the two groups.