Progression Of Infarction Research Articles

GDF11 inhibits cardiomyocyte pyroptosis and exerts cardioprotection in acute myocardial infarction mice by upregulation of transcription factor HOXA3

NLRP3 (Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3) inflammasome-mediated cardiomyocytes pyroptosis plays a crucial part in progression of acute myocardial infarction (MI). GDF11 (Growth Differentiation Factor 11) has been reported to generate cytoprotective effects in phylogenesis and multiple diseases, but the mechanism that GDF11 contributes to cardioprotection of MI and cardiomyocytes pyroptosis remains poorly understood. In our study, we first determined that GDF11 was abnormally downregulated in the heart tissue of MI mice and hypoxic cardiomyocytes. Moreover, AAV9-GDF11 markedly alleviated heart function in MI mice. Meanwhile, GDF11 overexpression also decreased the pyroptosis of hypoxic cardiomyocytes. PROMO and JASPAR prediction software found that transcription factor HOXA3 was predicted as an important regulator of NLRP3, and was confirmed by ChIP assay. Further analysis identifying GDF11 promoted the Smad2/3 pathway resulted in HOXA3 overexpression. Taken together, our study implies that GDF11 prevents cardiomyocytes pyroptosis via HOXA3/NLRP3 signaling pathway in MI mice.

Rapid Infarct Progression in Anterior Circulation Large Vessel Occlusion Ischemic Stroke Patients During Inter-Facility Transfer

IntroductionWe aimed to identify factors associated with rapid infarct progression during inter-facility transfer for endovascular thrombectomy evaluation and its impact on clinical outcomes. MethodsPatients with anterior circulation large artery occlusion within 24 h of onset transferred within our 17 hospital tele-stroke network were retrospectively analyzed. Patients were divided into fast progressors and slow progressors. Fast progressors were defined as CT ASPECTS score of ≥6 at the referring hospital (RH) and <6 at the hub hospital. Good clinical outcomes were defined as modified Rankin Scale score (mRS) 0–2 at 90 days. Demographic, clinical and radiologic variables associated with fast progressors and good clinical outcomes were identified using multivariable regression models. ResultsAmong the 190 patients, 44 (23%) patients underwent rapid infarct progression. Higher stroke severity at presentation [aOR, 1.096, 95% CI,1.023, 1.174; p = 0.009], presence of early ischemic changes (CT ASPECT 6-9) at the RH [aOR, 2.721, 95% CI, 1.22, 6.071; p = 0.014] were positively associated, whereas prior ischemic stroke [aOR, 0.272, 95% CI, 0.078, 0.948; p = 0.04] and higher collateral score (2,3,4) [aOR, 0.138, 95%CI, 0.059, 0.324, p=<0.0001] were negatively associated with rapid infarct progression. Fifty-eight (31%) transferred patients had good outcomes. After adjusting for reperfusion status, age [aOR, 0.96, 95% CI, 0.93, 0.98; p=<0.001], initial stroke severity [aOR, 0.87, 95% CI, 0.81, 0.93; p=<0.001], absolute rate of decrease in CT ASPECTS [aOR, 0.38, 95% CI, 0.19, 0.77; p = 0.007] and internal carotid artery (ICA) occlusion [aOR, 0.34, 95 %CI, 0.12, 0.94; p = 0.038] were negatively associated with good outcome. ConclusionHigher stroke severity, presence of early ischemic changes at the referring facility, absence of prior stroke, and poor collateral scores (CS 0-1) are the factors associated with rapid infarct progression in the telemedicine transfer cohort. Increasing age, higher stroke severity, higher absolute decrease in CT ASPECTS and ICA occlusion determine poor clinical outcomes.

Coexistence of transmural and lateral wavefront progression of myocardial infarction in the human heart

Introduction and objectivesAccording to the wavefront phenomenon described in the late 1970s, myocardial infarction triggered by acute coronary occlusion progresses with increasing duration of ischemia as a transmural wavefront from the subendocardium toward the subepicardium. However, whether wavefront progression of necrosis also occurs laterally has been disputed. We aimed to assess the transmural and lateral spread of myocardial damage after acute myocardial infarction in humans and to evaluate the impact of metoprolol on these. MethodsWe assessed myocardial infarction in the transmural and lateral dimensions in a cohort of 220 acute ST-segment elevation myocardial infarction (STEMI) patients from the METOCARD-CNIC trial (Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction). The patients underwent cardiac magnetic resonance imaging at 5 to 7 days and 6 months post-STEMI. ResultsOn day 5 to 7 post-STEMI cardiac magnetic resonance, there was a strong linear correlation between the transmural and lateral extent of infarction (delayed gadolinium enhancement) (r=-0.88; P<.001). Six months after STEMI, myocardial scarring (delayed gadolinium enhancement) was significantly less extensive in the transmural and lateral dimensions, suggesting that infarct resorption occurs in both. Furthermore, progression in both directions occurred both in patients receiving metoprolol and control patients, implying that myocardial salvage occurs both in the transmural and the lateral direction. ConclusionsOur findings challenge the assumption that irreversible injury does not spread laterally. A “circumferential” or multidirectional wavefront would imply that cardioprotective therapies might produce meaningful salvage at lateral borders of the infarct.This trial was registered at ClinicalTrial.gov (Identifier: NCT01311700).

USP47 promotes apoptosis in rat myocardial cells after ischemia/reperfusion injury via NF-κB activation.

An increasing number of studies have associated nuclear factor-κB (NF-κB) activation to the progression of myocardial infarction (MI). Multiple members of the ubiquitin-specific protease (USP) family regulate the NF-κB signaling pathway. This study attempted to investigate the function and underlying mechanism of USP family members in MI. Monocytes were isolated from peripheral blood samples of MI and healthy control, and the expression of several USP family members and NF-κB was examined. After USP47 knockdown or overexpression, cell apoptosis, related protein levels, and NF-κB promoter activity were measured. We found that USP47 and NF-κB expression was significantly increased in MI, and USP47 was positively correlated with NF-κB. In a rat H9c2 myocardial cell ischemia/reperfusion (I/R) injury model, USP47 expression was increased in a time-dependent manner. USP47 knockdown decreased I/R injury-induced apoptosis, with increased survivin and cytoplasmic NF-κB and decreased cleaved caspase-3 and nuclear NF-κB. USP47-induced apoptosis was potently counteracted by the NF-κB inhibitor, and cytoplasmic NF-κB was increased and nuclear NF-κB was decreased. Luciferase reporter showed that USP47 promotes NF-κB promoter activity. These results suggested that USP47 expression may be correlated with MI progression. USP47 knockdown attenuated myocardial cell I/R injury by inhibiting apoptosis.

Regenerative Potential of a Suspension and Spheroids of Multipotent Mesenchymal Stromal Cells from Human Umbilical Cord on the Model of Myocardial Infarction in Rats

Regenerative potential of multipotent mesenchymal stromal cells from the human umbilical cord (MMSC-UC) in the suspension and spheroid form was revealed during the progression of experimental small focal myocardial infarction in rats. In isoproterenol-induced myocardial infarction, foci of necrosis and inflammatory infiltrate and at later terms fibrosis foci were found mainly in the left ventricle of rat heart. In rats receiving MMSC-UC, destructive changes in the myocardium, fibrous scars, and inflammatory process were less pronounced. MMSC-UC also contributed to normalization of the morphofunctional parameters of the heart. Spheroids exhibited higher efficiency in comparison with cell suspension.

Monitoring Canine Myocardial Infarction Formation and Recovery via Transthoracic Cardiac Strain Imaging

Myocardial elastography (ME) is an ultrasound-based strain imaging method that aims to determine the degree of ischemia or infarction as a result of the change in the elastic properties of the myocardium. A survival canine model (n = 11) was employed to investigate the ability of ME to image myocardial infarction formation and recovery. Infarcts were generated by ligation of the left anterior descending coronary artery. Canines were survived and imaged for 4 days (n = 7) or 4 weeks (n = 4), allowing sufficient time for recovery via collateral perfusion. A radial strain-based metric, percentage of healthy myocardium by strain (PHMε), was developed as a marker for healthy myocardial tissue. PHMε was strongly linearly correlated with actual infarct size as determined by gross pathology (R2 = 0.80). Mean PHMε was reduced 1–3 days post-infarction (p < 0.05) at the papillary and apical short-axis levels; full infarct recovery was achieved by day 28, with mean PHMε returning to baseline levels. ME was capable of diagnosing individual myocardial segments as non-infarcted or infarcted with high sensitivity (82%), specificity (92%) and precision (85%) (area under the receiver operating characteristic curve = 0.90). The study therefore strengthens the ME premise that it can detect and assess myocardial infarction progression and recovery in vivo and could thus provide an important role in both disease diagnosis and treatment assesssment.

Prazosin blocks apoptosis of endothelial progenitor cells through downregulating the Akt/NF-κB signaling pathway in a rat cerebral infarction model.

Endothelial progenitor cells (EPCs) can enhance the recanalization of thrombosis during the progression of cerebral infarction. Prazosin plays a therapeutic role in expanding the peripheral vasculature and regulating infarction cardiosclerosis by inhibiting phosphoinositide signaling. However, the possible mechanisms underlying the therapeutic effects of prazosin have not been fully explored. The purpose of the present study was to analyze the anti-apoptotic effects of prazosin on EPCs in a rat cerebral infarction model. The results showed that prazosin treatment decreased apoptosis of EPCs. Prazosin treatment decreased the serum expression levels of the inflammatory factors, interleukin-1β and tumor necrosis factor-α in rats with cerebral infarctions as well as in EPCs in vitro. In addition, prazosin reduced the expression levels of Akt, NF-κB, phosphorylated (p)-Akt and p-NF-κB in EPCs and the middle cerebral artery of rats with cerebral infarction. These findings demonstrated that prazosin inhibited EPC apoptosis in the cerebral infarction rats through targeting the Akt/NF-κB signaling pathway. In conclusion, these results indicated that prazosin has a preventive effect on cerebral infarction by inhibiting EPC apoptosis and by inhibiting the inflammatory response in vitro and in vivo through regulating the Akt/NF-κB signaling pathway.

NFAT activating protein with ITAM motif 1 (NFAM1) is upregulated on circulating monocytes in coronary artery disease and potentially correlated with monocyte chemotaxis

Background and aimsCirculating monocytes have been proven to be critical mediators in the propagation and progression of atherosclerosis and myocardial infarction. The present study was designed to characterise a new transmembrane protein—NFAT activating protein with ITAM motif 1 (NFAM1)—on monocytes and uncover the potential effects and underlying mechanisms in coronary artery disease. MethodsMonocytes from a population of four controls, five stable coronary artery disease patients and five acute coronary syndrome patients were isolated for RNA sequencing. A potential monocyte biomarker molecule was discovered and then validated with a group of 79 controls, 70 stable coronary artery disease patients and 183 acute coronary syndrome patients. A stable cell line was generated as an in vitro model to determine chemotaxis migration and chemokine receptor expression. ResultsNFAM1 was identified through RNA sequencing analysis. The validation results confirmed that NFAM1 expression on monocytes was significantly increased by coronary artery disease status. A higher expression level of NFAM1 on classical and intermediate monocytes was observed compared with that on nonclassical monocytes. As shown in the in vitro cell model, knockdown of NFAM1 significantly attenuated chemotactic migration of monocytes by downregulating chemokine receptor expression and the p38 MAPK signalling pathway. Multivariable regression analysis of a group of 16 individuals suggested that NFAM1 was positively correlated with CCR2 expression. ConclusionsThe present study reported for the first time that distinctive alterations of NFAM1 expression on monocytes may correlate with atherosclerosis pathobiology and serve as a potential monocyte biomarker and therapeutic target for coronary artery disease.

Predictors and Functional Outcomes of Fast, Intermediate, and Slow Progression Among Patients With Acute Ischemic Stroke.

We aimed to delineate the determinants of the initial speed of infarct progression and the association of speed of infarct progression (SIP) with procedural and functional outcomes. From a prospectively maintained stroke center registry, consecutive anterior circulation ischemic stroke patients with large artery occlusion, National Institutes of Health Stroke Scale score ≥4, and multimodal vessel, ischemic core, and tissue-at-risk imaging within 24 hours of onset were included. Initial SIP was calculated as ischemic core volume at first imaging divided by the time from stroke onset to imaging. Among the 88 patients, SIP was median 2.2 cc/h (interquartile range, 0-8.7), ranging most widely within the first 6 hours after onset. Faster SIP was positively independently associated with a low collateral score (odds ratio [OR], 3.30 [95% CI, 1.25-10.49]) and arrival by emergency medical services (OR, 3.34 [95% CI, 1.06-10.49]) and negatively associated with prior ischemic stroke (OR, 0.12 [95% CI, 0.03-0.50]) and coronary artery disease (OR, 0.32 [95% CI, 0.10-1.00]). Among the 67 patients who underwent endovascular thrombectomy, slower SIP was associated with a shift to reduced levels of disability at discharge (OR, 3.26 [95% CI, 1.02-10.45]), increased substantial reperfusion by thrombectomy (OR, 8.30 [95% CI, 0.97-70.87]), and reduced radiological hemorrhagic transformation (OR, 0.34 [95% CI, 0.12-0.94]). Slower SIP is associated with a high collateral score, prior ischemic stroke, and coronary artery disease, supporting roles for both collateral robustness and ischemic preconditioning in fostering tissue resilience to ischemia. Among patients undergoing endovascular thrombectomy, the speed of infarct progression is a major determinant of clinical outcome.

Mild fever as a catalyst for consumption of the ischaemic penumbra despite endovascular reperfusion.

Cerebrovascular ischaemia is potentiated by hyperthermia, and even mild temperature elevation has proved detrimental to ischaemic brain. Infarction progression following endovascular reperfusion relates to multiple patient-specific and procedural variables; however, the potential influence of mild systemic temperature fluctuations is not fully understood. This study aims to assess the relationship between systemic temperatures in the early aftermath of acute ischaemic stroke and the loss of at-risk penumbral tissues, hypothesizing consumption of the ischaemic penumbra as a function of systemic temperatures, irrespective of reperfusion status. A cross-sectional, retrospective evaluation of a single-institution, prospectively collected endovascular therapy registry was conducted. Patients with anterior circulation, large vessel occlusion acute ischaemic stroke who underwent initial CT perfusion, and in whom at least four-hourly systemic temperatures were recorded beginning from presentation and until the time of final imaging outcome were included. Initial CT perfusion core and penumbra volumes and final MRI infarction volumes were computed. Systemic temperature indices including temperature maxima were recorded, and pre-defined temperature thresholds varying between 37°C and 38°C were examined in unadjusted and adjusted regression models which included glucose, collateral status, reperfusion status, CT perfusion-to-reperfusion delay, general anaesthesia and antipyretic exposure. The primary outcome was the relative consumption of the penumbra, reflecting normalized growth of the at-risk tissue volume ≥10%. The final study population comprised 126 acute ischaemic stroke subjects (mean 63 ± 14.5 years, 63% women). The primary outcome of penumbra consumption ≥10% occurred in 51 (40.1%) subjects. No significant differences in baseline characteristics were present between groups, with the exception of presentation glucose (118 ± 26.6 without versus 143.1 ± 61.6 with penumbra consumption, P = 0.009). Significant differences in the likelihood of penumbra consumption relating to systemic temperature maxima were observed [37°C (interquartile range 36.5 − 37.5°C) without versus 37.5°C (interquartile range 36.8 − 38.2°C) with penumbra consumption, P = 0.001]. An increased likelihood of penumbra consumption was observed for temperature maxima in unadjusted (odds ratio 3.57, 95% confidence interval 1.65 − 7.75; P = 0.001) and adjusted (odds ratio 3.06, 95% confidence interval 1.33 − 7.06; P = 0.009) regression models. Significant differences in median penumbra consumption were present at a pre-defined temperature maxima threshold of 37.5°C [4.8 ml (interquartile range 0 − 11.5 ml) versus 21.1 ml (0 − 44.7 ml) for subjects not reaching or reaching the threshold, respectively, P = 0.007]. Mild fever may promote loss of the ischaemic penumbra irrespective of reperfusion, potentially influencing successful salvage of at-risk tissue volumes following acute ischaemic stroke.

Targeting the pathways of regulated necrosis: a potential strategy for alleviation of cardio-cerebrovascular injury.

Apoptosis, necrosis and autophagy-dependent cell death are the three major types of cell death. Traditionally, necrosis is thought as a passive and unregulated form of cell death. However, certain necrosis can also occur in a highly regulated manner, referring to regulated necrosis. Depending on the signaling pathways, regulated necrosis can be further classified as necroptosis, pyroptosis, ferroptosis, parthanatos and CypD-mediated necrosis. Numerous studies have reported that regulated necrosis contributes to the progression of multiple injury-relevant diseases. For example, necroptosis contributes to the development of myocardial infarction, atherosclerosis, heart failure and stroke; pyroptosis is involved in the progression of myocardial or cerebral infarction, atherosclerosis and diabetic cardiomyopathy; while ferroptosis, parthanatos and CypD-mediated necrosis participate in the pathological process of myocardial and/or cerebral ischemia/reperfusion injury. Thereby, targeting the pathways of regulated necrosis pharmacologically or genetically could be an efficient strategy for reducing cardio-cerebrovascular injury. Further study needs to focus on the crosstalk and interplay among different types of regulated necrosis. Pharmacological intervention of two or more types of regulated necrosis simultaneously may have advantages in clinic to treat injury-relevant diseases.

Optimal Imaging at the Primary Stroke Center.

Optimal Imaging at the Primary Stroke Center.

A non-human primate model of stroke reproducing endovascular thrombectomy and allowing long-term imaging and neurological read-outs

Stroke is a devastating disease. Endovascular mechanical thrombectomy is dramatically changing the management of acute ischemic stroke, raising new challenges regarding brain outcome and opening up new avenues for brain protection. In this context, relevant experiment models are required for testing new therapies and addressing important questions about infarct progression despite successful recanalization, reversibility of ischemic lesions, blood–brain barrier disruption and reperfusion damage. Here, we developed a minimally invasive non-human primate model of cerebral ischemia (Macaca fascicularis) based on an endovascular transient occlusion and recanalization of the middle cerebral artery (MCA). We evaluated per-occlusion and post-recanalization impairment on PET-MRI, in addition to acute and chronic neuro-functional assessment. Voxel-based analyses between per-occlusion PET-MRI and day-7 MRI showed two different patterns of lesion evolution: “symptomatic salvaged tissue” (SST) and “asymptomatic infarcted tissue” (AIT). Extended SST was present in all cases. AIT, remote from the area at risk, represented 45% of the final lesion. This model also expresses both worsening of fine motor skills and dysexecutive behavior over the chronic post-stroke period, a result in agreement with cortical-subcortical lesions. We thus fully characterized an original translational model of ischemia–reperfusion damage after stroke, with consistent ischemia time, and thrombus retrieval for effective recanalization.

Determinants of cerebral radiological progression in Fabry disease

Background and aimIt is unclear which patients with Fabry disease (FD) are at risk for progression of white matter lesions (WMLs) and brain infarctions and whether enzyme replacement therapy (ERT)...

MicroRNA‑93 promotes angiogenesis and attenuates remodeling via inactivation of the Hippo/Yap pathway by targeting Lats2 after myocardial infarctionω.

Inactivation of the Hippo pathway protects the myocardium from cardiac ischemic injury. MicroRNAs (miRs) have been reported to play pivotal roles in the progression of myocardial infarction (MI). The present study examined whether miR-93 could promote angiogenesis and attenuate remodeling after MI via inactivation of the Hippo/Yes-associated protein (Yap) pathway, by targeting large tumor suppressor kinase 2 (Lats2). It was identified that transfection of human umbilical vein endothelial cells with miR-93 mimic significantly decreased Lats2 expression and Yap phosphorylation, increased cell viability and migration, and attenuated cell apoptosis following hypoxia/reoxygenation injury. Moreover, increased expression of miR-93 resulted in an improvement of cardiac function, promotion of angiogenesis and attenuation of remodeling after MI. Additionally, miR-93 overexpression significantly decreased intracellular adhesion molecule 1 and vascular cell adhesion protein 1 expression levels, as well as attenuated the infiltration of neutrophils and macrophages into the myocardium after MI. Furthermore, it was found that miR-93 overexpression significantly suppressed Lats2 expression and decreased the levels of phosphorylated Yap in the myocardium after MI. Collectively, the present results suggested that miR-93 may exert a protective effect against MI via inactivation of the Hippo/Yap pathway by targeting Lats2.

Calreticulin expression in human cardiac myocytes induces ER stress-associated apoptosis.

The global burden of heart failure following myocardial ischemia‐reperfusion (IR) injury is a growing problem. One pathway that is key to understanding the progression of myocardial infarction and IR injury is the endoplasmic reticulum (ER) stress pathway, which contributes to apoptosis signaling and tissue death. The role of calreticulin in the progression of ER stress remains controversial. We hypothesized that calreticulin induction drives proapoptotic signaling in response to ER stress. We find here that calreticulin is upregulated in human ischemic heart failure cardiac tissue, as well as simulated hypoxia and reoxygenation (H/R) and thapsigargin‐mediated ER stress. To test the impact of direct modulation of calreticulin expression on ER stress‐induced apoptosis, human cardiac‐derived AC16 cells with stable overexpression or silencing of calreticulin were subjected to thapsigargin treatment, and markers of apoptosis were evaluated. It was found that overexpression of calreticulin promotes apoptosis, while a partial knockdown protects against the expression of caspase 12, CHOP, and reduces thapsigargin‐driven TUNEL staining. These data shed light on the role that calreticulin plays in apoptosis signaling during ER stress in cardiac cells.

Roles and Mechanisms of Interleukin-12 Family Members in Cardiovascular Diseases: Opportunities and Challenges.

Cardiovascular diseases represent a complex group of clinical syndromes caused by a variety of interacting pathological factors. They include the most extensive disease population and rank first in all-cause mortality worldwide. Accumulating evidence demonstrates that cytokines play critical roles in the presence and development of cardiovascular diseases. Interleukin-12 family members, including IL-12, IL-23, IL-27 and IL-35, are a class of cytokines that regulate a variety of biological effects; they are closely related to the progression of various cardiovascular diseases, including atherosclerosis, hypertension, aortic dissection, cardiac hypertrophy, myocardial infarction, and acute cardiac injury. This paper mainly discusses the role of IL-12 family members in cardiovascular diseases, and the molecular and cellular mechanisms potentially involved in their action in order to identify possible intervention targets for the prevention and clinical treatment of cardiovascular diseases.

Early Recanalization in Patients With Cerebral Venous Thrombosis Treated With Anticoagulation.

Background and Purpose- The hypothesis that venous recanalization prevents progression of venous infarction is not established in patients with cerebral venous thrombosis (CVT). Evidence is also scarce on the association between residual symptoms, particularly headache, and the recanalization grade. We aimed to assess, in patients with CVT treated with standard anticoagulation, (1) the rate of early venous recanalization, (2) whether lack of early recanalization was predictor of parenchymal brain lesion progression, and (3) the prevalence and features of persistent headache according to the recanalization grade achieved. Methods- PRIORITy-CVT (Pathophysiology of Venous Infarction - Prediction of Infarction and Recanalization in CVT) was a multicenter, prospective, cohort study including patients with newly diagnosed CVT. Standardized magnetic resonance imaging was performed at inclusion (≤24 hours of therapeutic anticoagulation), days 8 and 90. Potential imaging predictors of recanalization were predefined and analyzed at each anatomical segment. Primary outcomes were rate of early recanalization and brain lesion progression at day 8. Secondary outcomes were headache (days 8 and 90) and functional outcome (modified Rankin Scale at days 8 and 90). Results- Sixty eight patients with CVT were included, of whom 30 (44%) had parenchymal lesions. At the early follow-up (n=63; 8±2 days), 68% (n=43) of patients had partial recanalization and 6% (n=4) full recanalization. Early recanalization was associated both with early regression (P=0.03) and lower risk of enlargement of nonhemorrhagic lesions (P=0.02). Lesions showing diffusion restriction (n=12) were fully reversible in 66% of cases, particularly in patients showing early venous recanalization. Evidence of new or enlarged hemorrhagic lesions, headache at days 8 and 90, and unfavorable functional outcome at days 8 and 90 were not significantly different in patients achieving recanalization. Conclusions- Venous recanalization started within the first 8 days of therapeutic anticoagulation in most patients with CVT and was associated with early regression of nonhemorrhagic lesions, including venous infarction. There was an association between persistent venous occlusion at day 8 and enlargement of nonhemorrhagic lesions.

Effect of Acute Myocardial Infarction on a Disintegrin and Metalloprotease with Thrombospondin Motif 13 and Von Willebrand Factor and Their Relationship with Markers of Inflammation.

Objectives Coagulation mechanisms and fibrinolytic assembly are important components role players of acute myocardial infarction (AMI) progression. Our study objective was to see the serial variations in the levels of Von Willebrand factor (VWF) and A Disintegrin and Metalloprotease with ThromboSpondin motif (ADAMTS13) over the course of AMI and to determine their relationship with the cardiovascular risk markers and the patient's clinical characteristics. Methods This project was done at the departments of Emergency Medicine, Physiology and Cardiac sciences of King Saud University Medical City. We studied ADAMTS13, VWF, fibrinogen, and CRP levels in 80 patients with AMI when patients were admitted; post AMI by 3-4 days and at follow-up of 3 months. We compared them with a control group consisting of 36 subjects. Results AMI had significantly lower levels of ADAMTS13 at AMI and after 3-4 days; at follow-up the difference in levels was nonsignificant, when compared with controls. Similarly, VWF levels were significantly higher in AMI and remained high even at follow-up compared to control subjects. VWF/ADAMTS13 ratio was also significantly higher at AMI and 3-4 days while at follow-up difference was nonsignificant compared to control subjects. Regression analysis between hsCRP and ADAMTS13 showed an inverse relationship (r = 0.376, p < 0.01), while correlation with VWF was significantly positive (r = 0.376, p < 0.01), while correlation with VWF was significantly positive (Conclusions Increased levels of VWF and reduced levels of ADAMTS13 activity may contribute to the pathogenesis of acute myocardial infarction and might prove to be important mediators of AMI progression.

Abstract WP280: A Potential Scoring System to Predict Infarct Progression During Inter Facility Transfer of Patients for Endovascular Thrombectomy Evaluation

Introduction: Current guidelines recommend CT ASPECTS≥6 as eligibility criteria for endovascular thrombectomy (EVT), a proven therapy for anterior circulation large vessel occlusion (ACLVO). Infarct progression during inter-facility transfer can render many patients ineligible for EVT. We developed a score utilizing clinical and imaging variables to predict infarct progression. Methods: Patients with ACLVO transferred from a referring hospital (RH) to our EVT capable center between August 2015 and December 2018 were reviewed. Significant predictors (p&lt;0.10) of infarct progression, defined as CT ASPECTS of ≥6 at RH to &lt;6 at hub, were identified using a logistic regression model. Regression coefficient estimates were used to score selected variables. The optimal cut-point was selected based on evaluated Youden index. Results: A total of 132 patients were analyzed. Score ranged from 0 to theoretical limit 18 (table 1): CTA collateral score (2/3/4=0, 0/1=3), Clot location (not ICA/M2=0, M2=2, ICA/M1=3), NIHSS (0-14=0, ≥15=5), use of antiplatelet by history (Yes=0, No=3), CT ASPECTS at RH (10=0, 6-9=2). Patients with score of ≥10.0 were more likely to have infarct progression (OR=22.15, 95% CI 4.99 - 98.35, p&lt;0.001). Conclusions: Our score utilizing clinical and imaging variables provides information on which patients with ACLVO may undergo infarct progression during inter-facility transfer. We plan to externally validate our findings in another hub and spoke network. This score may potentially aid decisions to develop stroke systems of care to triage patients with ACLVO within hub and spoke networks.