• Cardiac mechanics and incident ischemic stroke: the Cardiovascular Health Study

      Kamel, Hooman; Bartz, Traci M; Longstreth, W T; Elkind, Mitchell S V; Gottdiener, John; Kizer, Jorge R; Gardin, Julius M; Kim, Jiwon; Shah, Sanjiv (Springer Nature, 2021-08-30)
      Recent evidence indicates that our understanding of the relationship between cardiac function and ischemic stroke remains incomplete. The Cardiovascular Health Study enrolled community-dwelling adults ≥ 65 years old. We included participants with speckle-tracking data from digitized baseline study echocardiograms. Exposures were left atrial reservoir strain (primary), left ventricular longitudinal strain, left ventricular early diastolic strain rate, septal e' velocity, and lateral e' velocity. The primary outcome was incident ischemic stroke. Cox proportional hazards models were adjusted for demographics, image quality, and risk factors including left ventricular ejection fraction and incident atrial fibrillation. Among 4,000 participants in our analysis, lower (worse) left atrial reservoir strain was associated with incident ischemic stroke (HR per SD absolute decrease, 1.14; 95% CI 1.04-25). All secondary exposure variables were significantly associated with the outcome. Left atrial reservoir strain was associated with cardioembolic stroke (HR per SD absolute decrease, 1.42; 95% CI 1.21-1.67) and cardioembolic stroke related to incident atrial fibrillation (HR per SD absolute decrease, 1.60; 1.32-1.95). Myocardial dysfunction that can ultimately lead to stroke may be identifiable at an early stage. This highlights opportunities to identify cerebrovascular risk earlier and improve stroke prevention via therapies for early myocardial dysfunction.
    • Endovascular model of ischemic stroke in swine guided by real-time MRI

      Golubczyk, D; Kalkowski, L; Kwiatkowska, J; Zawadzki, M; Holak, P; Glodek, J; Milewska, K; Pomianowski, A; Janowski, M; Adamiak, Z; et al. (Springer Nature, 2020-10-14)
      Modeling stroke in animals is essential for testing efficacy of new treatments; however, previous neuroprotective therapies, based on systemic delivery in rodents failed, exposing the need for model with improved clinical relevance. The purpose of this study was to develop endovascular approach for inducing ischemia in swine. To achieve that goal, we used intra-arterial administration of thrombin mixed with gadolinium and visualized the occlusion with real-time MRI. Placement of the microcatheter proximally to rete allowed trans-catheter perfusion of the ipsilateral hemisphere as visualized by contrast-enhanced perfusion MR scans. Dynamic T2*w MRI facilitated visualization of thrombin + Gd solution transiting through cerebral vasculature and persistent hyperintensities indicated occlusion. Area of trans-catheter perfusion dynamically quantified on representative slice before and after thrombin administration (22.20 ± 6.31 cm2 vs. 13.28 ± 4.71 cm2 respectively) indicated significantly reduced perfusion. ADC mapping showed evidence of ischemia as early as 27 min and follow-up T2w scans confirmed ischemic lesion (3.14 ± 1.41 cm2). Animals developed contralateral neurological deficits but were ambulatory. Our study has overcome long lasting challenge of inducing endovascular stroke model in pig. We were able to induce stroke using minimally invasive endovascular approach and observe in real-time formation of the thrombus, blockage of cerebral perfusion and eventually stroke lesion.
    • Outcome after acute ischemic stroke is linked to sex-specific lesion patterns

      Bonkhoff, Anna K.; Schirmer, Markus D.; Bretzner, Martin; Hong, Sungmin; Regenhardt, Robert W.; Brudfors, Mikael; Donahue, Kathleen L.; Nardin, Marco J.; Dalca, Adrian V.; Giese, Anne-Katrin; et al. (Springer Nature, 2021-06-02)
      Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.