Stroke Alert March 2022

On Episode 14 of the Stroke Alert Podcast, host Dr. Negar Asdaghi highlights two articles from the March 2022 issue of Stroke: “Natural Course of Cerebral Cavernous Malformations in Children” and “Direct Oral Anticoagulants Versus Warfarin in Cerebral Venous Thrombosis (ACTION-CVT).” She also interviews Dr. Mohammad Anadani about his article “Magnitude of Blood Pressure Change After Endovascular Therapy and Outcomes.” Dr. Negar Asdaghi:                        1) Are direct oral anticoagulants a reasonable alternative to warfarin for treatments of patients with cerebral venous thrombosis? 2) What are the predictors of first and recurrent intracerebral hemorrhage in patients with cerebral cavernous malformation? 3) Is there an optimal blood pressure target after successful endovascular thrombectomy? We have the answers and much more in today's podcast. This is the latest in Stroke. Stay with us. Dr. Negar Asdaghi:                        Welcome to another incredibly informing Stroke Alert Podcast. My name is Negar Asdaghi. I'm an Associate Professor of Neurology at the University of Miami Miller School of Medicine and your host for the monthly Stroke Alert Podcast. The March 2022 issue of Stroke includes a number of papers published in conjunction with their oral presentation at the International Stroke Conference in New Orleans, from contemporary trends in the nationwide incidence of primary intracerebral hemorrhage, to disparities in Internet use among U.S. stroke survivors' implication for telerehabilitation during COVID-19 and beyond. I encourage you to review these timely topics in addition to listening to our podcast today. Later, in our interview section, I discussed the optimal blood pressure goal after endovascular therapy and the results of a subgroup analysis of the BP-TARGET randomized trials with Dr. Mohammad Anadani from the Department of Neurology at Washington University in St. Louis. But first with these two articles. Dr. Negar Asdaghi:                        Cerebral cavernous malformations, also referred to as cavernous angiomas, cavernomas, cav mals, or CCMs, are angiographically occult, low flow, vascular lesions with no large arterial inflow or venous outflow vessels. These are clusters of dilated sinusoidal vascular channels that are aligned by a single layer of endothelium without the normal surrounding vascular smooth muscles, and they lack the normal tight junctions between their endothelial cells. Cavernomas can be found in both children and adults. So, the question is, how do these lesions present, especially in children, and what is their natural course? Now, before we answer these questions, let's review a few important points about cavernomas and what is known about these lesions in the literature. Number one, cavernomas are acquired lesions. Although initially thought to be congenital, they're now known to be acquired as comparing by many reports of patients with normal MRI findings, who later developed a CCM. Number two, they're not always benign. While most of them can have a benign course, cerebral cavernomas can be a cause for headaches, seizure disorders and intracerebral hemorrhage, which is, of course, their most feared complication. Dr. Negar Asdaghi:                        Number three, though CCMs are rare vascular disorders with a prevalence of 0.6% in children and young adults, about a quarter of patients with a confirmed diagnosis of cerebral cavernous malformation are under the age of 18. And number four and finally, data seem to suggest that the risk of hemorrhage is potentially higher in the pediatric population than their adult counterparts. So, determining the natural course of CCMs and predictors of intracerebral hemorrhage is important for all patients, but especially important in the pediatric population. Now, in the current issue of the journal, in the paper titled "Natural Course of Cerebral Cavernous Malformations in Children: A Five-Year Follow-Up Study," a German group of investigators led by Dr. Alejandro Santos from the Department of Neurosurgery and Spine Surgery at University Hospital in Essen and colleagues studied the clinical presentation and predictors of intracerebral hemorrhage in their pediatric population over a 17-year study period. Dr. Negar Asdaghi:                        So, they identified 129 patients with a diagnosis of cerebral cavernous malformation that had baseline MRI imaging completed and at least one or more follow-ups during the study period. Now, some of these patients were treated surgically and some conservatively in the study. The mean age of their study was 10, and over 50% of their study population was male. Developmental venous anomalies, or DVAs, were detected in 15% of their study population, and 20% had brain stem cavernoma localization. Now, importantly, half of these kids, so that's 55.8% of their study population, presented with an intracerebral hemorrhage, and that's how their cavernomas were diagnosed. So, what were their top three findings? Dr. Negar Asdaghi:                        Number one, on the comparison of conservatively treated patients to those treated surgically, which was 37% of their cohort, they found that overall these two groups had comparable clinical characteristics and demographics with regards to sex, age, multiplicity of cavernomas, brain stem location, and family history of their lesions. But not surprisingly, those who were surgically treated were more likely to have presented with an intracerebral hemorrhage and less likely to be asymptomatic, meaning that their cavernoma was not an incidental finding as compared to those who were conservatively treated. Dr. Negar Asdaghi:                        Number two, when they looked at predictors of presentation with intracerebral hemorrhage, they found that family history of cavernomas and brain stem cavernomas were significant predictors of presenting intracerebral hemorrhage. Number three, when they excluded those who underwent surgery, the annual risk of hemorrhage for the overall untreated participants was 4.1%. However, we should note that this rate significantly varied based on certain characteristics of the patients. The risk of hemorrhage, or rather the risk of re-hemorrhage, was double this baseline, that is 8.1%, for those cavernomas that presented with a bleed at presentation. The annual rate of hemorrhage was equally high at 7.1% for brain stem cavernomas, and then this rate gradually declined for familial form cavernomas at 6.2% annual risk of hemorrhage and multiple cavernomas at 4.8%. And it went all the way down to 0.4% annual risk of hemorrhage for asymptomatic incidentally found cerebral cavernomas. So, in the multivariate analysis, presentation with an ICH remained an independent predictor of re-hemorrhage and cavernomas with a high hazard ratio of 14. That is 14-fold higher risk of hemorrhage in cavernomas that present with a bleed as compared to those that did not. Dr. Negar Asdaghi:                        Now, finally, on the association between DVAs and risk of hemorrhage, this study showed a possible reduced risk of hemorrhage in cavernomas that had associated DVAs, but this was not a statistically significant association. It is important to note that this finding is in keeping with the published studies in the adult population, but in contrast to the previously published data in the pediatric population. So, this association between presence of a developmental venous anomaly and cavernomas and the risk of subsequent hemorrhage needs to be furthered studied. So, what did we learn from this study? Pediatric patients with brain stem cavernomas and familial cavernomas have a higher risk of intracerebral hemorrhage as mode of presentation. The risk of re-hemorrhage is 14 times higher in cavernomas that present with an ICH as compared to cavernomas that did not bleed. And the probability of bleed tends to increase over time. Dr. Negar Asdaghi:                        Cerebral venous sinus thrombosis, or CVST, refers to thrombosis in the dural venous sinuses, cortical veins, deep cerebral veins, or a combination of these venous structures. CVST is an uncommon cause of stroke accounting for overall 1% of all strokes and can cause venous ischemic infarcts or intracerebral hemorrhage and importantly has a high morbidity and mortality if unrecognized and left untreated. Anticoagulation is generally the mainstay of therapy for CVST, which needs to be initiated as soon as possible, even in the presence of hemorrhage in the brain. The data regarding the choice of anticoagulation in CVST is generally extrapolated from randomized studies completed in patients with systemic venous thromboembolism, so conditions such as pulmonary emboli or deep venous thrombosis, and indicate that direct oral anticoagulants, or DOACs, are viable alternatives to traditional warfarin therapy in this patient population. This question was specifically studied in the RESPECT-CVT trial, which was a small European randomized trial that included 120 patients with cerebral vein thrombosis, randomized to either receiving dose adjusted warfarin or dabigatran at 150 milligram BID. Dr. Negar Asdaghi:                        The results of the study was published in JAMA Neurology in 2019 and showed that CVST patients treated with either dabigatran or warfarin were at low risk of recurrent venous thromboembolism, and they also showed a comparable safety profile in terms of risk of hemorrhage or mortality in patients treated with DOAC as compared to warfarin. But how do DOACs perform as compared to warfarin in routine practice is unknown. So, in this issue of the journal, in the study titled, "Direct Oral Anticoagulants Versus Warfarin in Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study," the ACTION-CVT investigators, led by Dr. Shadi Yaghi from the Department of Neurology at Brown University, aimed to compare the safety profile of DOACs to that of warfarin, in a multicenter international study that included 1025 imaging-confirmed CVST patients from multiple centers in the United States, Italy, Switzerland, and New Zealand. Dr. Negar Asdaghi:                        They had a number of exclusion criteria for this study, excluding patients with active cancer, those with a confirmed history of antiphospholipid antibody syndrome and those who were not treated with an oral anticoagulant. And after excluding these patients, it gave them their study sample of 845 CVST patients. So, what were their main findings? Number one, in keeping with a prior literature on CVST, these patients were young, their mean age was 44, and majority of them were women, so that was 67% of their cohort. And they found that a third of these patients were actually treated with a DOAC, and, in addition, another 15% received a DOAC at some times during their treatment course. Finding number two, the most common DOAC used in this population was apixaban, that was 66% of cases treated with a direct oral anticoagulant, followed by rivaroxaban in 18% of cases, and then dabigatran used in 13.5% of DOAC-treated cases. Dr. Negar Asdaghi:                        Important finding number three. A total of 27 patients had recurrent CVST, which also included patients with progression of their cerebral vein thrombosis on follow-up vascular imaging, and 17 patients had recurrent venous thromboembolism, and two had both. So, during their mean follow-up of 345 days, they had the rate of 5.68 recurrent venous thrombosis per 100 patient years. These rates were not different for DOAC-treated versus warfarin-treated patients in both unadjusted and adjusted models. Now, very important finding number four. When they looked at the rate of recanalization on follow-up imaging, for those in whom this information was available, partial or complete recanalization occurred in 86% of DOAC-treated patients versus 84% of warfarin-treated patients. This was not a statistically significant difference in the unadjusted or the adjusted models. Recanalization is, of course, an important determinant of outcomes in CVST and should be noted that recanalization is, of course, an important determinant of outcomes in CVST since persistent thrombosis through chronic raised ICP can potentially lead to a variety of neurological morbidities, such as chronic headache, chronic papilledema and increased risk of development of dural AV fistulas. Dr. Negar Asdaghi:                        Now, finally, in terms of safety profile, they had 31 hemorrhages, 23 intracranial, majority were symptomatic and 9 extracranial hemorrhages. The hazard ratio for hemorrhage or death was similar for DOAC- and warfarin-treated patients, again in the unadjusted and adjusted models. So, bottom line, in this large international cohort of patients with CVST treated with an oral anticoagulant in routine practice, patients treated with DOACs had similar clinical and radiographic outcomes and had a similar favorable safety profile when compared to those treated with warfarin. So, we stay tuned for the results of the ongoing randomized trials on this subject. Dr. Negar Asdaghi:                        What is the optimal blood pressure target after endovascular therapy? This is a commonly encountered question in routine clinical practice with a not-so-straightforward and easy answer. After a successful endovascular treatment, high systolic blood pressure targets are thought to be associated with increased risk of reperfusion injury and development of intraparenchymal hemorrhage, leading to worsening of clinical outcomes. Conversely, low blood pressure targets may worsen the ischemic penumbra, especially in the setting of incomplete perfusion. The current stroke guidelines recommendations regarding blood pressure control after endovascular treatment are mostly extrapolated from the post-thrombolysis studies. The BP-TARGET trial was a recently completed randomized study in France that aimed to assess the safety and efficacy of intensive blood pressure lowering, that is systolic blood pressure of less than 130, as compared to standard of care, that is systolic blood pressure between 130 to 185, after successful endovascular therapy in acute ischemic stroke. Dr. Negar Asdaghi:                        This was a neutral study, and the main results of the trial was published in early 2021 in Lancet Neurology. And if you missed it, well, as always, we're here with the Stroke Alert Podcast to fill in the gaps. So, we'll review the trial results with our podcast guest today, Dr. Mohammad Anadani, from the Department of Neurology at Washington University in St. Louis, who's also the first author of a paper in the current issue of the journal titled "Magnitude of Blood Pressure Change After Endovascular Therapy and Outcomes: Insight From the Blood Pressure-TARGET Trial." This was a post hoc analysis of the BP-TARGET trial, looking at the extent of blood pressure reduction and its implications of clinical outcomes. Welcome, Mohammad, thank you for joining us on the podcast today. Dr. Mohammad Anadani:            Thank you for having me. It's a pleasure to be here with you today. Dr. Negar Asdaghi:                        Thank you. So, blood pressure control is a really simple and yet extremely complicated topic when it comes to the collateral support before reperfusion therapies, and then, of course, the possibility of reperfusion injury post-thrombectomy in the setting of an ischemic stroke related to a large vessel occlusion. Can you please give our listeners an overview of the topic of blood pressure control in this setting? Dr. Mohammad Anadani:            Yes, absolutely. I totally agree. The topic of blood pressure control after, in patients with large vessel occlusion, is very complicated. And when we talk about blood pressure control, I think we should differentiate between pre-recanalization and post-recanalization. In the pre-recanalization period, the main focus should be to maintain adequate perfusion to ischemic penumbra to prevent infarct expansion. So, there is consensus that hypotension should be avoided at all costs pre-recanalization. When it comes to the post-reperfusion, here it gets a little bit more complicated. We do have a large body of evidence, as you mentioned, for the association between high blood pressure in the post-reperfusion period and the risk of poor outcome. What we don't know yet is if active reduction of blood pressure after reperfusion is beneficial. And that's why, as you mention, the American Heart Association guidelines just recommend a systolic blood pressure less than 180, just because of the lack of data to support the benefit of blood pressure reduction. Dr. Negar Asdaghi:                        Perfect. So, this was definitely the topic that the BP-TARGET trial set out to investigate. What is the optimal blood pressure target after successful revascularization therapy? Can you please tell us a little bit about the trial, the design and the inclusion criteria? Dr. Mohammad Anadani:            The Blood Pressure-TARGET trial, or BP-TARGET trial, aimed to assess the safety and efficacy of intensive blood pressure lowering treatment. The trial enrolled patients with anterior circulation large vessel occlusion, that is M1 or ICA occlusion, or tandem occlusion, which is both M1 and ICA occlusion. The patients who were treated with endovascular therapy and achieved successful reperfusion, and they defined successful reperfusion as modified treatment cerebral ischemia 2b to 3. And then after enrollment, the patients were randomized in one-to-one ratio into intensive blood pressure control, which is systolic blood pressure less than 130, and standard blood pressure control, which is systolic blood pressure less than 185. Now, these two cutoffs came in from some evidence that systolic blood pressure less than 130 is beneficial in these patients or this is the optimal cutoff for patients with successful reperfusion. For the standard group, the design of the trial, at the time of the design of the trial, that was the standard or recommended European guidelines, blood pressure group. And the study was conducted in France between June 2017 and September 2019. Dr. Negar Asdaghi:                        Thank you, Mohammad. So, I want to recap for our listeners, we're looking at a French study that was conducted in four centers, in France. And it's a very recent study, recently completed. The whole thing was completed over the past five years. So, very interesting because it's applicable to our current treatment models. And these were patients with a large vessel occlusion in the anterior circulation that had undergone thrombectomy. All have achieved a successful revascularization, as you defined, TICI 2b or C or TICI 3, and then they were randomized to either standard of care in terms of post-thrombectomy blood pressure control or the intensive group, which was under systolic blood pressure of 130. Did I recap that correctly? Dr. Mohammad Anadani:            Correct. Dr. Negar Asdaghi:                        Perfect. So, now we're ready for the primary outcome. So, what was the primary outcome of the trial? Dr. Mohammad Anadani:            The primary outcome was any radiographic intraparenchymal hemorrhage that was seen on CT within 24 hours to 36 hours after successful reperfusion. Dr. Negar Asdaghi:                        This is interesting, Mohammad, this is a different primary outcome than we're used to in a usual randomized trial that commonly uses a modified Rankin scale of usually at 90 days. Do you have any insight as to why a radiographic outcome was chosen for this particular study, and obviously what would be fine as part of the trial? Dr. Mohammad Anadani:            Yes. So, the main reason why the study investigator chose this as a primary outcome was because really the benefit of, or at least what is thought to be the benefit from systolic blood pressure reduction, is to lower intraparenchymal hemorrhage or the risk of intraparenchymal hemorrhage. So, to assist the efficacy of this intensive blood pressure lowering, the first thing we expect to see is lower intraparenchymal hemorrhage. So, when you have your target as intraparenchymal hemorrhage, it truly requires much smaller sample size than having functional outcome as the primary outcome. Dr. Negar Asdaghi:                        Okay, perfect. And I think we're ready to hear the results for the main BP-TARGET trial. Dr. Mohammad Anadani:            The results of the trial were disappointing for people who were interested in this topic. The primary outcome, which, again, was an intraparenchymal hemorrhage, occurred in 42% of patient intensive arm and 43% of patient the standard arm. And there was no difference in the risk of intraparenchymal hemorrhage between the two groups. Dr. Negar Asdaghi:                        Well, I think you can phrase it as disappointing, or more room to understand the pathophysiology and also onto bigger and better trials. And so I want to now move on the current paper in this issue of the journal, which is a post hoc analysis of the trial. Can you tell us a little more about your study? Dr. Mohammad Anadani:            In our study, we wanted to study the blood pressure as dynamic target. So, we wanted to see if there is any association between blood pressure change from baseline with the functional and safety outcome after endovascular therapy. And also we wanted to understand the shape of the association. In other words, to see, is there a point after which the blood pressure reduction becomes helpful? So, to do that, we did this post hoc analysis of the BP-TARGET trial, and we only enrolled patients who had more than 50% of planned blood pressure measurements. And then we defined systolic blood pressure change as the difference in the mean achieved blood pressure in three different time points: zero to one hour, one to six hours, and six to 24 hours minus the baseline systolic blood pressure. And here we considered the end-of-procedure blood pressure as the baseline systolic blood pressure. Dr. Negar Asdaghi:                        All right. So, I want to recap what you mentioned before we hear what you found in the study. So, really, blood pressure, as you noted, is a dynamic factor. It's not just a target, but other words, is how fast you're reducing it, in what timeframe after endovascular thrombectomy, and also how much. So, as an example, as we were discussing this earlier, before we did the podcast recording, is if you started a systolic blood pressure at 190 and then reduced that patient quickly to 130, is that the same as if starting blood pressure was 150, and then you reduce it to, again, 130? So, delta, or the magnitude of change in blood pressure, and also time intervals, that how long after thrombectomy you were able to reduce that blood pressure, are all important factors in terms of determining the outcome. That's a nice summary of what this current study aimed to do. Perfect. So, with that, we're ready to hear the results of your study. Dr. Mohammad Anadani:            We included 267 patients, 137 in the intensive arm and 130 patients in the standard arm. And then, when we compared patients who had poor outcome at 90 days to patients who had good outcome at 90 days, we found that the patient who had poor outcome had less systolic pressure reduction, meaning these patients had less systolic pressure reduction compared to the baseline than the patient who had good outcome. And then, when we controlled for other confounders, their association remained significant, especially for the one- to six-hour period and six- to 24-hour period. And the same results were when we had our outcome as intraparenchymal hemorrhage, we found the same results. The patient who had intraparenchymal hemorrhage had less systolic blood pressure reduction than patients who did not have intraparenchymal hemorrhage. And, again, the association remained significant even after we adjusted for possible confounders, like age, the degree of recanalization, and the stroke severity. Dr. Mohammad Anadani:            And then we wanted to see, if we looked at the blood pressure change as categorical variable, meaning we want to see if there is a difference between large systolic blood pressure reduction compared to minimum or no systolic blood pressure reduction. So, we divided the systolic blood pressure reduction into three categories: the minimal, which was just zero to 10 systolic blood pressure reduction; the moderate, which was 10 to 20; and large, which was more than 20 millimeter mercury systolic blood pressure reduction. And when we looked at that, a patient who had more than 20 millimeter mercury systolic blood pressure reduction had significantly lower risk of poor outcome than patients who had no systolic blood pressure reduction or just minimal systolic blood pressure reduction. And the difference was striking. There were the patients who had more than 20 systolic blood pressure reduction, they had almost 62% lower risk or lower odds of having poor outcome than a patient who did not have significant systolic blood pressure reduction. Dr. Negar Asdaghi:                        These are some very interesting findings. Let me try and to summarize this for our listeners and make sure that I understood the study results correctly. So, in other words, if we had a patient that at the end of a successful revascularization treatment, say, had a systolic blood pressure of 150, and that was reduced to 140, so there's a 10 millimeter mercury difference, that patient, in this particular study, had a higher risk for development of intracerebral hemorrhage than the person that finished at 180, so finished endovascular therapy at 180 millimeter of mercury. But then with rapid reduction, we dropped the blood pressure to, say, for example, 140, so that 40 millimeter of mercury of reduction carried a higher weight or higher impact on reduction of intracerebral hemorrhage than the absolute target of blood pressure, because your results did not look at which category were these patients under, were they under intensive category or standard, but they looked at just the magnitude of that drop, which showed a bigger implication on effective blood pressure reduction on outcomes. Dr. Mohammad Anadani:            Yeah, that is correct. Now, the primary outcome for our study and really what we want to look at here is the functional outcome, more than the intraparenchymal hemorrhage. And, like you said, if we have, let's say, patients who started with 160 and they dropped to 120 or started with 180 and they dropped to 150, these patients had better functional outcome than patients who started, let's say, with 160 and remained 160 or even their blood pressure increased after reperfusion. We did not look at absolute numbers, but we did look at if the patients were presented, let's say, above 180 or patient presented less than 180, and both of these patients had the same, or both of these groups had the same results, meaning systolic blood pressure seems to be beneficial for both of these patients. And also we looked at the patients who were in the standard arm or in the patients who were in the intensive arm, also both of them have the same results. The systolic blood pressure reduction remained associated with poor outcome. Dr. Negar Asdaghi:                        Mohammad, the current American Heart Association guidelines and also the European stroke guidelines both recommend a target systolic blood pressure of under 180 or 185 after successful recanalization. What do you think the optimal target blood pressure should be based on BP-TARGET trial and based on your post hoc analysis? Dr. Mohammad Anadani:            Yeah, that's a difficult question. We learn from the BP-TARGET trial, that's lowering systolic blood pressure is safe. And our study added to that, that significant reduction, especially in the first hour after reperfusion therapy, may be beneficial because patient had lower risk of poor outcome. However, I don't think we will have a one number that we will be able to say, this is the optimal blood pressure that fits all patients. I think the optimal blood pressure needs to be tailored to individual patient based on their admission blood pressure, based on their comorbidities, and also based on the degree of reperfusion. I don't think patients who have TICI 2b, for example, should be treated exactly the same as patients who had TICI 3. Dr. Negar Asdaghi:                        So, a lot still to come on this topic, and we are still learning. So, on that topic, can you tell us a little bit about the currently ongoing randomized trials on the topic of blood pressure controlled post-thrombectomy? Dr. Mohammad Anadani:            Yes. I think there are three main trials that are ongoing now and trying to assess the safety and efficacy also of intensive blood pressure reduction. The first trial is the Second Enhanced Control of Hypertension and Thrombectomy Stroke Study, or ENCHANTED2 study. And this study is being conducted now in China. And it's comparing systolic blood pressure less than 120 target to systolic blood pressure less than 180. And the study has the primary outcome here, is the shift in mRS score at 90 days. The study is estimated to be completed in 2023, so, hopefully next year, we will have some results. The second study is the Outcome in Patients Treated With Intraarterial Thrombectomy - optiMAL Blood Pressure Control, or OPTIMAL-BP. And this study is being conducted in South Korea, and it's comparing systolic blood pressure target of less than 140 to systolic blood pressure target of less than 180. Dr. Mohammad Anadani:            And the primary outcomes of this study are mRS zero to two at 90 days and symptomatic intracerebral hemorrhage. The study here is estimated to be completed in 2024. And the last trial is the Blood Pressure After Endovascular Stroke Therapy-II, or the BEST-II trial. And this is being conducted here in the U.S. and comparing three different blood pressure cohorts: less than 160 and less than 140 as the experimental group to less than 180 as the standard group. And the primary outcome of this study is final infarct volume. And also the co-primary outcome is utility-weighted mRS at 90 days. And this study is estimated to be completed next year, in 2023. Dr. Negar Asdaghi:                        So, a diverse group of randomized trials from Korea, China, and the United States. Hopefully, we'll have a lot more answers in the next two years then on this topic. So, just the last few minutes of our recording here. Mohammad, can you please summarize for our listeners, what should be our top two takeaway messages from your study and what we know from collectively in the field on the topic of blood pressure control post-thrombectomy? Dr. Mohammad Anadani:            I think the main home message that one, we found a leaner association between blood pressure change after endovascular therapy and poor functional outcome, and two, effective and significant systolic blood pressure reduction, which we defined in our study as a more than 20 millimeter mercury in the first hour after endovascular therapy, is potentially beneficial, and these patients had significantly lower risk of poor outcome than the patient who did not have significant blood pressure reduction. Dr. Negar Asdaghi:                        Thank you so much, Dr. Mohammad Anadani. Thank you for joining on the podcast today, and we look forward to having you back and covering more of your work in the future. Dr. Mohammad Anadani:            Thank you for having me, and I look forward to learning more about the Stroke studies from your podcast. Dr. Negar Asdaghi:                        Thank you. Dr. Negar Asdaghi:                        And this concludes our podcast for the March 2022 issue of Stroke. Please be sure to check out this month's table of contents for the full list of publications, including a series of Focused Updates on the topic of health equity and reduction of disparities in stroke, organized by Dr. Bruce Ovbiagele. It's hard to believe that we're already in March, and coming off the heels of one of our largest cerebrovascular annual meetings, the International Stroke Conference, which coincidentally concurrently happened with one of the biggest sports events of the year, the 2022 Winter Olympics in Beijing. Now, what do these two very different events have in common? Well, I think they both represent the extraordinary stories of talent and grit on the world stage. So, let's end our Stroke podcast with an inspirational story of the Olympian swimmer Yusra Mardini. Dr. Negar Asdaghi:                        In August 2015, after her family home was invaded and destroyed in the Syrian civil war, the 17-year-old Yusra and her sister, Sarah, fled Syria to Beirut, Istanbul, and finally İzmir, in Turkey, where they managed to squeeze onto a dingey crossing the Mediterranean to the Greek island of Lesbos. Carrying 20 people, rather than just six or seven, they found their boat sinking less than 30 minutes into their journey. Yusra, Sara, and another woman were the only ones on board who knew how to swim. Fighting for their life and that of the other refugees on board, they would swim the cold open water of the heavy seas for three and a half hours before reaching the shore. Less than a year later, Yusra became one of the top 10 athletes worldwide to qualify and compete in the 2016 Summer Olympics, as part of the first refugee Olympic athletes team. She won the opening heat of women 100-meter butterfly race, but did not make it to the podium in the Olympic Games. And that is, of course, only part of her story. Dr. Negar Asdaghi:                        Very much like the story of many scientists, doctors, engineers, and staff who make the international stroke meeting possible. Many stories are not celebrated on a podium, but nevertheless are the essence of the success of our stroke community. So, wherever you are in the field of neurosciences, whatever the challenge, and however cold the waters, know that while we don't share the same border, the same flag, or even a common language, together we push the field of cerebrovascular disorders forward. And, as always, we stay alert with Stroke Alert. Dr. Negar Asdaghi:         This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, visit AHAjournals.org.