Early Reperfusion Research Articles

Early improvement in left ventricular microvascular flow post sonothrombolysis is associated with better left ventricular systolic function in st elevation myocardial infarction patients

Abstract Background/Introduction Acute coronary syndromes are the main cause of death worldwide and the timely application of proper therapy is critical for patient outcome. However, even when state of the art treatment is implemented, significant no-reflow phenomenon may occur. In this scenario, sonothrombolysis, which consists of a continuous infusion of an ultrasound-enhancing agent associated with high-energy intermittent ultrasound impulses, may restore cardiac microcirculation and improve left ventricular (LV) systolic function. Purpose We aimed to evaluate LV segmental microvascular flow, LV mechanics and function in patients with ST-elevation myocardial infarction (STEMI) after sonothrombolysis therapy and evaluate whether an early (immediately post percutaneous coronary intervention – PCI or PCI+Sonothrombolysis) improvement in myocardial microvascular flow could predict better LV systolic function at 1-month. Methods STEMI patients receiving conventional treatment (PCI with or without previous fibrinolytic therapy) were randomized to sonothrombolysis (therapy group - TG) or conventional treatment (control group - CG). This study included 143 patients (interim analysis) who compose the HUBBLE I databank (High-intensity Ultrasonic impulses and microbuBBles to Limit the Extent of acute myocardial infarction I) and were randomized from two clinical trials (NCT04732091 and NCT02410330): CG, N=74 and TG, N=69 patients. There were 25 patients treated previously with fibrinolytic therapy (14 in CG and 11 in TG) and the percentage of left anterior descending artery as culprit vessel was similar between groups (59 vs. 54%, P=0.482). Sonothrombolysis was initiated after patient admission to the emergency room and continued after PCI for a total of 50 minutes. Echocardiography was carried out immediately after PCI or PCI+Sonothrombolysis and at 1-month for assessing LV ejection fraction (LVEF) and perfusion score index (PSI) in contrasted imaging and global longitudinal strain (GLS) in 2D imaging, that was presented in [module]. Results Demographic characteristics, cardiovascular risk factors and echocardiographic variables immediately after PCI or PCI+Sonothrombolysis were similar between groups (P>0.05). At 1-month follow up, TG presented higher LVEF (46.4±10.5 vs. 50.9±11.1%, P=0.018) and GLS (13.0±3.6 vs. 14.9±4.3%, P=0.008) and lower PSI (1.56±0.4 vs. 1.39±0.3, P=0.007) and number of segments with perfusion defects (5.8±3.7 vs. 4.6±3.3, P=0.050) compared with CG. There was a negative correlation between early PSI and 1-month LVEF (r=-0.701, p<0.0001). Conclusions The preliminary data indicates that sonothrombolysis can be an effective adjuvant treatment in STEMI patients previously treated or not with fibrinolytic therapy, contributing to a better myocardial microvascular flow and LV systolic performance. Early myocardial microvascular reperfusion improvement can predict whether cardiac function will improve in this setting.

Direct Oral Anticoagulants versus Vitamin K Antagonists for the management of left ventricular thrombus after myocardial infarction: A meta-analysis

Abstract Background/Introduction Left ventricular (LV) thrombus formation is not an uncommon complication after acute myocardial infarction (AMI) in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario remains poorly-defined. Purpose The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with Vitamin K antagonists (VKAs) for the management of LV thrombus following AMI. Methods A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after MI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and random-effects meta-analyses were conducted to synthesize pooled ORs. Results Eight studies comprising a total of 605 patients were included (Table). DOACs were associated with an almost 2-fold higher likelihood for achieving thrombus resolution compared to VKAs (pooled OR 1.95 [1.25-3.04]; p =0.003, I2 =0 %), while they achieved a 70% lower risk for systemic embolism (pooled OR 0.30 [0.12-0.75]; p =0.01, I2 =0%). The use of DOACs was associated with a 54% lower risk for bleeding compared to VKAs (pooled OR 0.46 [0.26-0.84]; p =0.01, I2 =0 %). Overall, patients receiving DOACs had a 63% lower risk to reach the composite outcome of any bleeding, systemic embolism, cardiovascular hospitalization, or all-cause death, compared with patients using VKAs (pooled OR 0.37 [0.23-0.60]; p <0.0001, I2 =0%) (Figure). Conclusion DOACs appear to have a more favorable efficacy and safety profile compared to VKAs for the management of LV thrombus following AMI.Graphical abstractTable

Neuro- and vasoprotective potential of neuropeptide Y2 receptor agonist, NPY13-36, against transient focal cerebral ischemia in spontaneously hypertensive rats

Numerous in vitro and in vivo experimental studies indicate that neuropeptide Y Y2 receptors (Y2R) are potential targets for neuroprotective therapy, including neuroprotection against ischemic stroke in healthy rats. Since stroke in humans is typically associated with comorbidities and long-term hypertension is the most common comorbidity leading to stroke, this study aimed to assess the neuroprotective potential of the Y2R agonist NPY13–36 in the rats with essential hypertension (SHR) subjected to 90 min middle cerebral artery suture occlusion with subsequent reperfusion (MCAOR). The cerebrocortical microflow in the ischemic focus and penumbra was continuously monitored with a Laser-Doppler flowmeter. NPY13–36 (10 μg/6 μl physiological saline solution) was administered intracerebroventricularly (i.c.v.) during ischemia or early reperfusion. The infarct area (triphenyltetrazolium chloride staining), behavioral tests (gait, mobility, and sensorimotor functions), and the response of the cerebrocortical microcirculation in the penumbra to hypercapnia and to the inhibition of the synthesis of nitric oxide were studied. Our results demonstrate that administration of NPY13-36 reduces the size of the infarct, improves motor functions, and restores microcirculatory response to the blockade of nitric oxide synthase when administered during reperfusion. The novelty of this study is a finding of the vasoprotective effect of NPY13-36 in brain ischemia/reperfusion. Moreover, this study provides evidence of the beneficial effects of NPY13-36 in animals with essential hypertension and indicates that Y2R ligands may be promising candidates for treating the ischemic brain in the case of this disease.

Dual antiplatelet including clopidogrel and aspirin, cardiac MRI, and speckle tracking echocardiography parameters in ST-elevation myocardial infarction patients

Coronary artery disease is the medical term for atherosclerotic coronary disease, which causes the coronary arteries to constrict and inadequately provide blood to the heart. ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, & unstable angina are the three conditions that comprise acute coronary syndromes. Studied cases with STEMI have been advised to take several drugs in addition to early reperfusion treatment, such as antiplatelet & anticoagulant medications. The goal of antiplatelet medications is to stop platelets from aggregating together. Oral dual antiplatelet medication, which combines lifetime aspirin with an oral P2Y12 receptor inhibitor, is the main antiplatelet therapy in STEMI. Aspirin ought to be administered to all studied cases immediately following diagnosis, and a low dose of treatment should be continued indefinitely. Heart mortality and severe adverse cardiac events are strongly and independently correlated with the presence & size of scarred tissue seen by cardiac MRI. Scar transmurality measured by cardiac MRI in studied cases with healed infarcts & ventricular dysfunction predicts patient survival and functional recovery following revascularization. Patients with heart illnesses that have a history of ST-segment elevation myocardial infarction may be at risk for unfavorable results based on echocardiographic evaluation of cardiac structure & function. Because speckle tracking echocardiography (STE) is quick and simple to do, it can be used in acute settings as well. It can be used for further risk stratification following revascularization, before invasive coronary angiography, or in cases when a diagnosis is unclear, if available.

Therapeutic potential of mesenchymal stromal cells on morphological parameters in the hippocampus of rats with brain ischemia-reperfusion modeling

Ischemic stroke is an extremely important pathology with high mortality, in which more than 50 % of patients with occlusion of the main vessels remain disabled, despite early reperfusion therapy by thrombolysis or thrombectomy. As part of the regenerative strategy, stem cell transplantation in ischemic stroke became a new impetus. Cell therapy with the use of mesenchymal stromal cells demonstrated encouraging results regarding endogenous mechanisms of neuroregeneration in response to ischemic damage to brain structures. The aim of the research is to study the influence of mesenchymal stromal cells of various genesis, lysate of mesenchymal stromal cells obtained from Wharton’s jelly umbilical cord and citicoline on the dynamics of morphological changes in the hippocampal CA1 region of rats with acute cerebral ischemia-reperfusion according to light microscopy and micromorphometry data. The experiment was carried out using 200 male Wistar rats, which were subjected to ischemia-reperfusion by reversible 20-minute bilateral occlusion of the internal carotid arteries. Animals with modeled pathology were intravenously transplanted with mesenchymal stromal cells of various genesis (from Wharton’s jelly of the human umbilical cord, human and rat adipose tissue), and rat embryonic fibroblasts, lysate of mesenchymal stromal cells and citicoline were injected. Histological analysis of rat brain sections was performed on the 7th and 14th day of the experiment. Statistical analysis was performed using “Statistica 6.0” (StatSoft® Snc, USA). The significance of differences was assessed using the Student’s t-test and the nonparametric Mann-Whitney U test. During the study, it was found that modeled ischemia-reperfusion in rats caused almost complete degeneration of the structure of the pyramidal layer of hippocampal CA1 region, gave uniformity to the structure of the radiant layer, infiltration of microglia, contributed to the disruption of the arrangement of apical dendrite bundles and narrowing of blood vessels as a result of perivascular edema. Also, the modeled pathology reduced the total number of neuronal nuclei in the hippocampal CA1 area, the overwhelming majority of which had signs of pathological changes. Transplantation of mesenchymal stromal cells of various origins, lysate of mesenchymal stromal cells and citicoline contributed to a significant increase in the number of neuronal nuclei in the hippocampal CA1 zone and nuclei that did not undergo pathological changes. The most positive effect was found in the transplantation of mesenchymal stromal cells from human Wharton’s jelly-derived cells. Thus, both in the subacute and recovery periods of ischemic stroke in rats, the transplantation of human Wharton’s jelly-derived mesenchymal stromal cells was significantly surpassed the reference drug citicoline in its ability to reduce the number of pathologically changed nuclei by 1.5 times (p<0.05). At the same time, the number of pathologically unchanged nuclei significantly exceeded the number of nuclei with signs of karyorrhexis and karyopyknosis, so it would be advisable to use mesenchymal stromal cells of various genesis, lysate or citicoline in conditions of acute cerebral ischemia-reperfusion, taking into account their ability to reduce the volume of the infarct. In the future, an injectable drug will be created from the most effective culture of mesenchymal stromal cells in terms of cerebroprotective properties for cell therapy of patients with acute ischemic stroke.

Reperfusion therapy and risk of post-stroke delirium

ABSTRACT Objectives Delirium is a common and serious post-stroke complication. Early reperfusion by ameliorating brain damage could potentially prevent delirium after ischemic stroke, but the impact of this therapy on delirium remains unclear. We aimed to explore the association between reperfusion therapy (RT) and post-stroke delirium. Methods We retrospectively analyzed data from the PRospective Observational POLIsh Study on post-stroke delirium. Symptoms of delirium were examined during the first 7 days after admission and a diagnosis of delirium was made using Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. We used logistic regression to examine the association between RT and delirium. Results We included 301 acute stroke patients (median age: 77; median NIHSS: 14; 55.1% female). In the whole group of patients, RT was associated with a lower odds of delirium (34.2% vs 44.8%; adjusted OR: 0.56, 95% CI: 0.32–0.96, p = 0.035). There was a significant interaction between RT and pre-stroke cognitive status. As a result, RT was associated with a lower odds of delirium in patients without premorbid cognitive decline (28.8% vs 48.2%; adjusted OR: 0.34, 95% CI: 0.17–0.66, p = 0.002) and a higher odds of delirium in patients with pre-stroke cognitive decline (72.7% vs 41.0%; adjusted OR: 3.55, 95% CI: 1.03–12.20, p = 0.040). Discussion The association between RT and delirium is modified by pre-stroke cognitive status. In patients without cognitive decline, RT is associated with a lower likelihood of delirium. Delirium should be considered as a relevant outcome in future controlled trials.

Routine beta-blocker therapy after acute coronary syndromes: The end of an era?

Beta-blocker therapy, a treatment burdened by side effects including fatigue, erectile dysfunction and depression, was shown to reduce mortality and cardiovascular events after acute coronary syndromes (ACS) in the pre-coronary reperfusion era. Potential mechanisms include protection from ventricular arrhythmias, increased ischaemia threshold and prevention of left ventricular (LV) adverse remodelling. With the advent of early mechanical reperfusion and contemporary pharmacologic secondary prevention, the benefit of beta-blockers after ACS in the absence of LV dysfunction has been challenged. The present narrative review discusses the contemporary evidence based on searching the PubMed database and references in identified articles. Recently, the REDUCE-AMI trial-the first adequately powered randomized trial in the reperfusion era to test beta-blocker therapy after myocardial infarction with preserved left ventricular ejection fraction (LVEF)-showed no benefit on the composite of all-cause death or myocardial infarction over a median 3.5-year follow-up. While the benefit of beta-blockers in patients with reduced LVEF remains undisputed, their value in post-ACS patients with mildly reduced systolic function (LVEF 41%-49%) has not been studied in contemporary randomized trials; in this setting, observational studies have suggested a reduction in cardiovascular events with these agents. The adequate duration of beta-blocker therapy remains unknown, but observational data suggests that any mortality benefit may be lost beyond 1-12 months after ACS in patients with LVEF >40%. We believe that there is sufficient evidence to abandon routine beta-blocker prescription in post-ACS patients with preserved LV systolic function.

Direct Oral Anticoagulants versus Vitamin K Antagonists for the Management of Left Ventricular Thrombus after Myocardial Infarction: A Meta-analysis

Left ventricular (LV) thrombus formation remains a post-acute myocardial infarction (AMI) complication even in the modern era of early reperfusion. The optimal anticoagulation regimen in this clinical scenario is poorly defined. The present meta-analysis sought to investigate the efficacy and safety profile of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) for the management of LV thrombus after AMI. A systematic literature review was conducted in electronic databases to identify studies reporting efficacy and safety outcome data regarding the use of DOACs versus VKAs for patients with LV thrombus after AMI. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and random-effects meta-analyses were conducted to synthesize pooled ORs. Eight studies comprising a total of 605 patients were included. DOACs were associated with an almost twofold higher likelihood of thrombus resolution compared with VKAs (pooled OR 1.95 [1.25 to 3.04], p = 0.003, I2 = 0%), and decreased the risk of systemic embolism by 70% (pooled OR 0.30 [0.12 to 0.75]; p = 0.01, I2 = 0%). The use of DOACs was associated with a 54% lower risk of bleeding compared with VKAs (pooled OR 0.46 [0.26 to 0.84], p = 0.01, I2 = 0%). Overall, patients receiving DOACs had a 63% lower risk of reaching the composite outcome of safety and efficacy compared with patients using VKAs (pooled OR 0.37 [0.23 to 0.60], p <0.0001, I2 = 0%). In conclusion, DOACs appear to have a more favorable efficacy and safety profile compared with VKAs for the management of LV thrombus related to AMI.

Controlled automated reperfusion of the whole body after cardiac arrest: Device profile of the CARL system.

Cardiac arrest is associated with high mortality rates and severe neurological impairments. One of the underlying mechanisms is global ischemia-reperfusion injury of the body, particularly the brain. Strategies to mitigate this may thus improve favorable neurological outcomes. The use of extracorporeal cardiopulmonary membrane oxygenation (ECMO) during CA has been shown to improve survival, but available systems are vastly unable to deliver goal-oriented resuscitation to control patient's individual physical and chemical needs during reperfusion. Recently, controlled automated reperfusion of the whoLe body (CARL), a pulsatile ECMO with arterial blood-gas analysis, has been introduced to deliver goal-directed reperfusion therapy during the post-arrest phase. This review focuses on the device profile and use of CARL. Specifically, we reviewed the published literature to summarize data regarding its technical features and potential benefits in ECPR. Peri-arrest, mitigating severe IRI with ECMO, might be the next step toward augmenting survival rates and neurological recovery. To this end, CARL is a promising extracorporeal oxygenation device that improves the early reperfusion phase after resuscitation.

Unveiling the role of long non-coding RNA MALAT1: a comprehensive review on myocardial infarction.

Myocardial infarction (MI) stands at top global causes of death in developed countries, owing mostly to atherosclerotic plaque growth and endothelial injury-induced reduction in coronary blood flow. While early reperfusion techniques have improved outcomes, long-term treatment continues to be difficult. The function of lncRNAs extends to regulating gene expression in various conditions, both physiological and pathological, such as cardiovascular diseases. The objective of this research is to extensively evaluate the significance of the lncRNA called Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in the development and management of MI. According to research, MALAT1 is implicated in processes such as autophagy, apoptosis, cell proliferation, and inflammation in the cardiovascular system. This investigation examines recent research examining the effects of MALAT1 on heart function and its potential as a mean of diagnosis and treatment for post- MI complications and ischemic reperfusion injury.

Abstract Tu143: Hsp90β Facilitates Cell Death During Acute Cardiac Ischemia/Reperfusion Injury

Myocardial infarction (MI), which caused 110,000 deaths in America in 2020, occurs following a complete blockage (ischemia) in one or more of the coronary arteries. Additionally, clearing the blockage (reperfusion) causes massive cell death, resulting in permanent tissue damage in the heart. Preventing cell death in IR injury is key to improving patient outcome in this disease. Molecular chaperones have emerged as promising targets in IR injury due to their pro-survival functions. However, the role of Hsp90β, the most abundant and constitutively active chaperone, in IR injury has not been fully elucidated. Therefore, we generated a cardiac-specific Hsp90β conditional knockout (cKO) mouse model to address it. To our surprise, current preliminary results suggest that cardiac-specific Hsp90β ablation reduces myocardial damage during IR injury, as Hsp90β cKO mice showed reduced infarct size compared to control. Opening of the mitochondrial permeability transition pore (mPTP) is the major driver of necrotic cell death during early reperfusion. Isolated mitochondria from the hearts of Hsp90β cKO mice show decreased sensitivity to mPTP opening during calcium overload, suggesting that it may be one of the cardioprotective mechanisms mediated by Hsp90β ablation. The Hsp90β cKO hearts also display an anti-apoptotic shift of the BAX/BCL2 apoptotic rheostat, suggesting the heart will be more resistant to apoptotic cell death during late reperfusion phase as well. Findings from this study will help us understand the role of Hsp90β in cell death activation during IR injury. In the future, we plan to investigate the underlying protective mechanisms mediated by Hsp90β ablation.

Abstract We070: The role of neutrophil YAP in cardiac inflammation and injury

Background: There is a growing appreciation that neutrophils demonstrate plasticity, not unlike the macrophage, and can modulate both inflammation and repair following organ injury. Neutrophils are rapidly recruited to the heart after acute myocardial infarction (MI) and participate in cardiac inflammation and remodeling. Nevertheless, mechanisms regulating neutrophil function during heart injury remain largely unknown. Research Question/Aim: Previous work demonstrated that Yes-Associated Protein (YAP) regulates macrophage function during heart injury. However, whether YAP regulates neutrophil function in any context, including reperfused MI (I/R), remains unexplored. Approach: We generated neutrophil-specific YAP KO mice (MRP8 Cre ) and subjected them to I/R to elicit inflammation and injury. Cell-based experiments were performed using primary isolated mouse neutrophils. We utilized flow cytometry, single-cell RNAseq, and histological and biochemical assays to investigate underlying mechanisms. Results: Neutrophils isolated from the blood and heart of WT mice subjected to I/R revealed increased YAP expression. Compared to control mice, neutrophil YAP KO hearts had decreased infarct size after 24 hours reperfusion, and better cardiac function after 2 weeks. Single-cell RNAseq of heart leukocytes indicated suppression of inflammatory, migratory, and superoxide production pathways in YAP KO neutrophils. Characterization of neutrophils by flow cytometry indicated a shift toward reparative polarization in YAP KO mice during early reperfusion. Bone marrow-derived neutrophils (BMDNs) from KO mice had attenuated inflammatory gene expression and ROS production compared to control cells. Pharmacological inhibition of YAP using verteporfin produced comparable results. Ongoing experiments are investigating how YAP modulates neutrophil inflammatory function, and will determine the therapeutic potential of targeted YAP inhibition for I/R injury. Conclusion: These results suggest that YAP regulates neutrophil function during I/R injury in the heart and that suppression of neutrophil YAP affords cardioprotection.

HERMES-24 Score Derivation and Validation for Simple and Robust Outcome Prediction After Large Vessel Occlusion Treatment.

Clinicians need simple and highly predictive prognostic scores to assist practical decision-making. We aimed to develop a simple outcome prediction score applied 24 hours after anterior circulation acute ischemic stroke treatment with endovascular thrombectomy and validate it in patients treated both with and without endovascular thrombectomy. Using the HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) collaboration data set (n=1764), patients in the endovascular thrombectomy arm were divided randomly into a derivation cohort (n=430) and a validation cohort (n=441). From a set of candidate predictors, logistic regression modeling using forward variable selection was used to select a model that was both parsimonious and highly predictive for modified Rankin Scale (mRS) ≤2 at 90 days. The score was validated in validation cohort, control arm (n=893), and external validation cohorts from the ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke; n=1066) and INTERRSeCT (Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography; n=614). In the derivation cohort, we selected 2 significant predictors of mRS ≤2 (National Institutes of Health Stroke Scale score at 24 hours and age [β-coefficient, 0.34 and 0.06]) and derived the HERMES-24 score: age (years)/10+National Institutes of Health Stroke Scale score at 24 hours. The HERMES-24 score was highly predictive for mRS ≤2 (c-statistic 0.907 [95% CI, 0.879-0.935]) in the derivation cohort. In the validation cohort and the control arm, the HERMES-24 score predicts mRS ≤2 (c-statistic, 0.914 [95% CI, 0.886-0.944] and 0.909 [95% CI, 0.887-0.930]). Observed provability of mRS ≤2 ranged between 3.1% and 3.4% when HERMES-24 score ≥25, while it ranged between 90.6% and 93.0% when HERMES-24 score <10 in the derivation cohort, validation cohort, and control arm. The HERMES-24 score also showed c-statistics of 0.894 and 0.889 for mRS ≤2 in the ESCAPE-NA1 and INTERRSeCT populations. The post-treatment HERMES-24 score is a simple validated score that predicts a 3-month outcome after anterior circulation large vessel occlusion stroke regardless of intervention, which helps prognostic discussion with families on day 2.

Correction to: Association of Intravenous Alteplase, Early Reperfusion, and Clinical Outcome in Patients With Large Vessel Occlusion Stroke: Post Hoc Analysis of the Randomized DIRECT-MT Trial.

Correction to: Association of Intravenous Alteplase, Early Reperfusion, and Clinical Outcome in Patients With Large Vessel Occlusion Stroke: Post Hoc Analysis of the Randomized DIRECT-MT Trial.

Reteplase versus Alteplase for Acute Ischemic Stroke

BackgroundAlteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear.MethodsWe randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset.ResultsA total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P=0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20).ConclusionsAmong patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.)

Early REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION): Study protocol of a phase III trial.

Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00.

Complications and Management of Myocardial Infarction in Hypertensive Patients: A Review

Background: Myocardial infarction (MI) and hypertension are cardiovascular conditions that frequently coexist and influence each other. Hypertension not only increases the risk of MI but also complicates its clinical management. Therefore, it is crucial to understand the complications arising from this condition and the effective management strategies. Objectives: This systematic review aims to identify and analyze common complications in hypertensive patients experiencing MI and evaluate the optimal management approaches based on the latest literature. Methods: A literature search was conducted in electronic databases such as PubMed, Scopus, and Google Scholar using relevant keywords like "myocardial infarction," "hypertension," "complications," and "management." Articles published in the last five years were selected to ensure the most current information. Inclusion criteria included observational studies, clinical trials, and systematic reviews relevant to the topic. Data were extracted and analyzed descriptively. Results: Of the 1500 articles identified, 45 studies met the inclusion criteria. Major complications found in hypertensive patients with MI included heart failure, arrhythmias, stroke, and left ventricular dysfunction. The most effective management approaches included appropriate use of antihypertensive medications, early reperfusion interventions, and a multidisciplinary approach to controlling cardiovascular risk factors. The use of ACE inhibitors, beta-blockers, and aldosterone antagonists proved to have significant benefits in reducing morbidity and mortality. Conclusions: Complications of myocardial infarction in hypertensive patients require comprehensive and coordinated management. Effective management involves a combination of pharmacological and non-pharmacological therapies focusing on optimal blood pressure control and prevention of further complications. Further research is needed to explore more specific and personalized management strategies in this population.

Safety and Efficacy of Conscious Sedation Versus General Anesthesia for Distal Vessel Thrombectomy

BACKGROUND AND OBJECTIVES: Anesthesia modality for endovascular thrombectomy (EVT) for distal and medium vessel occlusions remains an open question. General anesthesia (GA) may offer advantages over conscious sedation (CS) because of reduced patient movement facilitating catheter navigation, but concerns persist about potential delays and hypotension affecting collateral circulation. METHODS: In our prospectively maintained stroke registry from December 2014 to July 2023, we identified patients with distal and medium vessel occlusions defined as M2, M3, or M4 occlusion; A1 or A2 occlusion; and P1 or P2 occlusion, who underwent EVT for acute ischemic stroke. We compared patients who received CS with those who received GA. Primary outcomes were early neurological improvement (ENI), successful reperfusion, first-pass effect, and good outcome at 90 days. Secondary outcomes included intracerebral hemorrhage, subarachnoid hemorrhage, and 90-day mortality. RESULTS: Of 279 patients, 69 (24.7%) received GA, whereas 193 (69.2%) received CS. CS was associated with higher odds of ENI compared with GA (odds ratio [OR] 2.59, 95% CI [1.04-6.98], P &lt; .05). CS was also associated with higher rates of successful reperfusion (OR 2.33, 95% CI [1.11-4.93], P &lt; .05). CS nonsignificantly trended toward lower rates of mortality (OR 0.51, 95% CI [0.2-1.3], P = .16). No differences in good outcome at 90 days, intracerebral hemorrhage, subarachnoid hemorrhage, or first-pass effect were seen. CONCLUSION: The use of CS during EVT seems to be safe and feasible with regard to successful recanalization, hemorrhagic complications, clinical outcome, and mortality. In addition, it may be associated with a higher rate of ENI. Further randomized studies in this specific EVT subpopulation are warranted.

Thrombus extraction in acute ischemic stroke: three years of experience at the regional vascular center

From a modern perspective, the key to successful treatment of ischemic stroke is early reperfusion with systemic thrombolytic therapy and thrombus extraction. Thrombectomy is the only reliable method of recanalization in patients with thrombosis of a large cerebral artery. Despite the fact that thrombus extraction has proven its effectiveness in the treatment of acute ischemic stroke in a number of large randomized trials, there are still issues that have not been fully studied, on which there are controversial opinions among specialists. For instance, there is different information about whether direct thrombectomy or thrombus extraction after systemic thrombolysis is more effective and safer. Moreover, in accordance with modern procedures for providing care to patients with acute cerebral circulatory disorders, patients admitted in the «therapeutic window» should receive intravenous thrombolytic therapy even if thrombectomy is planned. Based on the analysis of 164 thrombus extractions in patients with acute ischemic stroke admitted to the regional vascular center in 2020–2023, the results of direct thrombus extraction and staged reperfusion (systemic thrombolytic therapy + thrombectomy) were compared. It has been found that compared to direct thrombus extraction, staged reperfusion provides more frequent achievement of 2b-3 recanalization (71.83 % and 78.49 %, respectively), accompanied by lower mortality (45 % and 23.66 %, respectively) and more frequent achievement of Rankin 0–2 functional status at the time of discharge (48.72 % and 61.96 %, respectively). The worst results were observed among patients with vascular occlusion in the vertebrobasilar basin, at TICI 0-2a and the age of patients over 80 years.

Transcriptional Profiling Underscores the Role of Preprocurement Allograft Metabolism and Innate Immune Status on Outcomes in Human Liver Transplantation.

The adverse effects of ischemia-reperfusion injury (IRI) remain a principal barrier to a successful outcome after lifesaving orthotopic liver transplantation (OLT). Gene expression during different phases of IRI is dynamic and modified by individual exposures, making it attractive for identifying potential therapeutic targets for improving the number of suitable organs for transplantation and patient outcomes. However, data remain limited on the functional landscape of gene expression during liver graft IRI, spanning procurement to reperfusion and recovery. Therefore, we sought to characterize transcriptomic profiles of IRI during multiple phases in human OLT. We conducted clinical data analyses, histologic evaluation, and RNA sequencing of 17 consecutive human primary OLT. We performed liver allograft biopsies at 4 time points: baseline (B, before donor cross-clamp), at the end of cold ischemia (CI), during early reperfusion (ER, after revascularization), and during late reperfusion (LR). Data were generated and then recipients grouped by post-OLT outcomes categories: immediate allograft function (IAF; n = 11) versus early allograft dysfunction (EAD; n = 6) groups. We observed that CI (vs B) modified a transcriptomic landscape enriched for a metabolic and immune process. Expression levels of hallmark inflammatory response genes were higher transitioning from CI to ER and decreased from ER to LR. IAF group predominantly showed higher bile and fatty acid metabolism activity during LR compared with EAD group, while EAD group maintained more immunomodulatory activities. Throughout all time points, EAD specimens exhibited decreased metabolic activity in both bile and fatty acid pathways. We report transcriptomic profiles of human liver allograft IRI from prepreservation in the donor to posttransplantation in the recipient. Immunomodulatory and metabolic landscapes across ER and LR phases were different between IAF and EAD allografts. Our study also highlights marker genes for these biological processes that we plan to explore as novel therapeutic targets or surrogate markers for severe allograft injury in clinical OLT.