American Heart Association

Monthly Archives: February 2019

Infarct Growth in the Early Time Windows: The Time Paradox

Ravinder-Jeet Singh, MBBS, DM

Broocks G, Rajput F, Hanning U, Faizy TD, Leischner H, Schön G, et al. Highest Lesion Growth Rates in Patients With Hyperacute Stroke: When Time Is Brain Particularly Matters. Stroke. 2018;50:189–192.

Infarct growth has become a topic of intense discussion in the current endovascular era, mainly due to its likely impact on stroke care models. A core theme of these models is decision to transport or treat eligible patients immediately, but also to limit futile transfers (drip-and-ship patient) and futile recanalization (mothership patient). The big question is: Which patient will grow their infarct during transfer and thus become ineligible for intervention on arrival to a comprehensive stroke center (futile transfers), and who will grow their infarct after imaging to derive no or minimal benefit from recanalization (futile recanalization)? Various clinical and imaging predictors have been proposed to predict infarct growth, including age, time, collateral status, etc. The study by Broocks et al. suggests that time is an important determinant of infarct growth, but its relation to lesion growth is rather counterintuitive, with early presenters having higher infarct growth compared to late presenters.

Infection Impact on Stroke Outcome Beyond Hospital Discharge

Elena Zapata-Arriaza, MD
@ElenaZaps

Boehme AK, Kulick ER, Canning M, Alvord T, Khaksari B, Omran S, et al. Infections Increase the Risk of 30-Day Readmissions Among Stroke Survivors: Analysis of the National Readmission Database. Stroke. 2018;49:2999–3005.

Infection is a most frequent medical complication after stroke. It is well recognized that acute stroke induces both the central nervous system and peripheral inflammatory responses, and, infection during stroke admission increases acute and longer-term inflammatory responses, complicating stroke outcomes. However, up to now, clinical trials with prophylactic aim in infection after stroke have failed. Therefore, stroke and infection develop a negative feedback between them.

Based on the known association between infection and stroke outcomes, the authors performed a weighted analysis of the federally managed 2013 National Readmission Database to assess the relationship between infection during a stroke hospitalization and 30-day readmission (30dRA) among ischemic stroke survivors. The main goal of this paper was to confirm the relation between stroke infection and 30dRA. The novelty of the paper is the identification of stroke associated infection as a predictor of readmission, not only as the most frequent cause of a new hospitalization. The authors employed the International Classification of Disease Ninth Revision [ICD-9] codes to identify ischemic stroke patients with ICD-9 codes present in the first diagnostic position ischemic stroke (referred as primary ischemic stroke patients) and patients with ischemic stroke code at any diagnostic position (referred as all ischemic stroke patients). The primary outcome, 30dRA, was classified as any hospitalization occurring within the 30-day postdischarge window and classified into planned or unplanned readmissions using previously validated ICD-9 codes. Secondary outcomes, 7dRA and 60dRA, were also assessed and were classified as any hospitalization occurring within the 7 days, or 60 days, postdischarge window.

ISC 2019: Acute Endovascular Treatment Oral Abstracts III

International Stroke Conference
February 6–8, 2019

Deepak Gulati, MD

There is uncertainty about factors affecting collaterals, natural course of collaterals and the type of anesthesia during thrombectomy. The session started with the detailed analysis of the GOLIATH trial to identify predictors of collateral circulation grade, infarct growth at 24hrs and the effect of collaterals on clinical outcome. The GOLIATH trial was a single center RCT comparing GA vs CS in acute patients with ELVO within 6 hours. Successful reperfusion was better in GA vs CS (76.9% vs 60.3, p=0.04). This study categorized Grade 2 ASTIN Collateral grading into 2- and 2+ based on <50% or >50% defect in ischemic territory, respectively. The anesthesia protocol included MAP>70 but could not be achieved in 26% of the entire population (35.4% in GA vs 15.9% in CS). Patient were also found to be hypocarbic with median ET CO2 of 33mmHg. There is no effect of collaterals noticed on clinical outcomes. Infarct growth is found to be associated with the use of pressor use (phenylephrine). This study concluded that sedation induced intraprocedural BP drop has a deleterious effect on collateral circulation and may not be reversed by IV pressor administration.

ISC 2019: Opening a Window and Throwing Out the Clock

International Stroke Conference
February 6–8, 2019

Session: “Extending the Thrombolytic Time Window to 9 Hours for Acute Ischemic Stroke using Perfusion Imaging Selection – The Final Result”

Kara Jo Swafford, MD

Henry Ma, PhD, from Monash University in Melbourne, Australia, presented the final results of the EXtending the time for Thrombolysis in Emergency Neurological Deficits (EXTEND) trial at the 2019 International Stroke Conference in Honolulu, HI, on Friday, February 8. The EXTEND trial was a randomized, multicenter, double-blinded, placebo-controlled phase III trial of intravenous alteplase versus placebo designed to test the hypothesis that the time window for treatment could be as long as 9 hours from stroke onset (including wake-up stroke patients with unknown last known well). Recruitment for the EXTEND trial halted in June 2018 after the WAKE-UP trial demonstrated benefit from imaging-guided intravenous thrombolysis in acute stroke patients with unknown last known well. The WAKE-UP trial used MRI rather than CT perfusion for patient selection.

ISC Session: “Medical Therapy for Symptomatic Carotid Stenosis: Time for Modern Data”

International Stroke Conference
February 6–8, 2019

Deepak Gulati, MD

There has been significant improvement in medical management in the last decade leading to various options in 2019 as compared to the era when earlier clinical trials on carotid stenosis were performed.

Dr. Seemant Chaturvedi from the University of Maryland presented on multi-modal treatment of carotid stenosis. Statins plays an important role by reducing LDL being the primary focus of treatment. In the SPARCL study, 32% risk reduction was seen with statins. The cardioprotective mechanisms of physical activity includes psychological, anti-arrhythmic, anti-thrombotic, anti-atherosclerotic and improved hemodynamics. Various studies/guidelines support the encouragement of regular exercise as a stroke prevention strategy and should be emphasized to patients. Physical activity is often found to be a ‘neglected prescription.’ Exercise volumes of 150 min/week of moderate-intensity or 75 min/week of vigorous-intensity aerobic exercise further reduce CVD mortality. Several diets have been proposed for CV risk reduction, including the DASH diet and Mediterranean diet. Being DM as one of the major vascular risk factor, stroke physicians should be aware of recent advances in anti-hyperglycemic drugs. Some newer antihyperglycemic agents have an FDA indication for reduction of either CV death or CV events. The use of dual antiplatelet therapy has been increasing based on the CHANCE and POINT trial. Some of the newer strategies include PCSK9 inhibitors, ezetimibe and TG reduction. Our current management of symptomatic carotid stenosis is based on the NASCET trial published in 1991. Given the recent advances in multimodal medical treatment, there appears to be a strong need of new clinical trials in patients with carotid stenosis.

ISC Session: “What’s Old Is New Again: Neuroprotection for Stroke in 2019”

International Stroke Conference
February 6–8, 2019

Robert W. Regenhardt, MD, PhD
@rwregen

Moderators: Jean Claude Baron, Andrew Demchuk

The first talk, by Nerses Sanossian, was titled “Neuro-protection in the Pre-hospital Setting.” Sanossian began by introducing the ischemic cascade in which there are rapid changes over minutes to hours (O2 depletion, energy failure, terminal depolarization, ion homeostasis failure), secondary changes over minutes to days (excitotoxicity, SD-like depolarizations, disturbance of ion homeostasis), and delayed changes over days to weeks (inflammation, apoptosis). While no neuro-protective agent has proven successful in phase 3 clinical trials, he asserts that these agents still hold promise. Reconsideration of mechanistic targets is important as there has been a shift in treatment paradigm with thrombectomy now the priority for LVO strokes. As these patients are collected from locations of symptom onset, transported to thrombectomy capable hospitals, and admitted for acute care, when is the best time to offer a neuro-protective agent? Future trials must balance the timing against the cost. An agent could be administered pre-hospital, post-arrival/pre-imaging, post-tPA, pre/during transfer if needed, pre-thrombectomy, or post-thrombectomy. There are unique considerations for each timepoint. In the pre-hospital setting, consent can be difficult, there is no imaging available, agents should be safe in ICH, have no interaction with tPA, easily stored in ambulances, administration should be easy (avoid pumps and compounding), agents should be effective despite fewer patients recanalizing, and have robust experimental data at early time points. In-hospital initiation allows standard consent, imaging is available (could tailor agent to stroke subtype), pharmacies can store and dispense agents, agents can be combined with recanalization (improved delivery to target tissue and opportunity for targeting reperfusion injury and hemorrhagic transformation), and patients can be more carefully selected after imaging for those most likely to benefit.

ISC Session: “Stroke, Anticoagulants and Antidotes”

International Stroke Conference
February 6–8, 2019

Kat Dakay, DO

As direct oral anticoagulants have gained increasingly widespread use and expanding indications, there has been a growing interest in their efficacy, pharmacokinetics, and reversal. At ISC 2019, an invited symposium focusing on this topic was co-moderated by Dr. Bruce Ovbiagele, MD, MSc, MAS, MBA, from USCF and Dr. Kazunori Toyoda, MD, from the National Cerebral and Cardiovascular Center in Osaka, Japan.

Pictured from left to right, speakers and moderators of the “Stroke, Anticoagulants and Anti-dotes” session at the International Stroke Conference, are: Dr. Kazunori Toyoda, Dr. David Seiffge, Dr. Ashkan Shoamanesh, Dr. Maurizio Paciaroni, Dr. Bruce Ovbiagele, and Dr. Truman Milling.

Pictured from left to right, speakers and moderators of the “Stroke, Anticoagulants and Antidotes” session at the International Stroke Conference, are: Dr. Kazunori Toyoda, Dr. David Seiffge, Dr. Ashkan Shoamanesh, Dr. Maurizio Paciaroni, Dr. Bruce Ovbiagele, and Dr. Truman Milling.

ISC Session: “Cost Effective Stroke Interventions in Low and Middle Income Countries” — Left Behind or a Different Reality?

International Stroke Conference
February 6–8, 2019

Victor J. Del Brutto, MD

I had the pleasure to attend the session “Cost Effective Stroke Interventions in Low and Middle Income Countries” moderated by Dr. Salvador Cruz-Flores during the International Stroke Conference held in Honolulu, HI, last week.

Dr. Sheila Martins, founder of the Brazilian Stroke Network, initiated the session, sharing her experience on the implementation of dozens of stroke centers across Brazil as part of a National Stroke Project, as well as the accomplishment of stroke telemedicine, rehabilitation programs and initiatives to increase stroke awareness among the population. Martins emphasized the mortality reduction achieved by such government policies, as well as the future expectations of creating systems able to deliver acute endovascular therapies and establishing a national stroke registry.

ISC: Report on a Positive Study of the EXTEND Trial

International Stroke Conference
February 6–8, 2019

Richard Jackson, MD

I’m writing to you from ISC reporting on an important breakthrough in the hyperacute treatment of ischemic strokes. Dr. Henry Ma reported on a positive study of the EXTEND trial evaluating extending the thrombolytic time window to 9 hours for acute ischemic stroke using perfusion imaging selection.

This was a trial performed in Australia, New Zealand, and Thailand using MRI or CT based perfusion-mismatch with inclusion criteria of  a core <70 mL and a mismatch >10 mL.  The median NIHSS was 11 with a median last known normal (LKN) of 10 hours, median core infarct of 4 mL, and median mismatch of 79 mL.  10% of the of patients had LKN of 4-6 hours, 25% 6-9 hours, and 65% wake up stroke.  72% of the patients had an LVO but did not receive thrombectomy. Despite this, there was a RR 1.44 for MRS 0-1 at 1 month and RR 1.4 for MRS 0-2 at 3 months. There was a RR 2.6 for early improvement in the NIHSS 0-8 points and 51% had 90% recanalization and reperfusion with no difference in death at 90 days. There was a comparable ICH ratio to previous trials with 6% but a RR of 6.9 which did not negate the clinical benefit.

This is a great step towards advanced imaging evaluation of ischemic lesions and reperfusion. One which we have all thought about and been waiting for.

ISC Session: “One Size Fits All? Models for Thrombectomy Systems of Care”

International Stroke Conference
February 6–8, 2019

Robert W. Regenhardt, MD, PhD
@rwregen

Moderators: Carmelo Graffagnino, Edward Jauch

The first talk, “Challenges in Patient Access,” by Carmelo Graffagnino discussed the system problems we face in the thrombectomy era. There are many system models that can be used to organize a region for the care of acute stroke patients. The models that worked well in the past allowed rapid access to tPA, but as thrombectomy expertise is a scarcer resource, there are new challenges. Graffagnino described two cases: one that showed how the system can work perfectly and another that highlighted limitations as a patient experienced severe delay in transferring to the thrombectomy capable center. Some of these limitations are difficult to predict and even more difficult to fix from the perspective of physicians, such as lack of helicopter and ambulance availability.