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Thrombolytic Therapy - Top 30 Publications

Managing Venous Thromboembolic Disease On-Call.

Managing venous thromboembolic disease on-call requires the interventional radiologist consider not only potential risk and benefit to the patient but also available resources in the IR suite as well as throughout the hospital, such as intensive care monitoring during treatment. We demonstrate how our practice manages these on-call cases ranging from deep venous thrombosis to acute pulmonary embolism and decide which patients need emergent treatment and which can undergo delayed intervention during working hours. In all cases, an adequate preprocedural clinical assessment is crucial.

Acute Limb Ischemia.

Acute limb ischemia is technically defined as ischemia of the lower extremities lasting 14 days or less. The condition affects between 15 and 26 persons per 100,000 each year in the United States. The associated morbidity and mortality is extremely high, with 1-year mortality rates reported at over 40%. Acute limb ischemia is 20 times more common in the lower extremities than the upper extremities. Both interventional radiologists and vascular surgeons bring unique skills to the table in caring for these patients, and therefore should approach the care of these patients in a multidisciplinary manner to ensure the best outcomes for each patient. Patients should be classified according to the Rutherford classification scale for acute limb ischemia. Catheter-directed thrombolysis can be a viable treatment alternative for these patients, offering a minimally invasive option to patients with outcomes similar to surgery. It is important to know the presentation, physical examination, risks and benefits, as well as the techniques and equipment required to treat patients with acute lower limb ischemia.

Contemporary risk model for inhospital major bleeding for patients with acute myocardial infarction: The acute coronary treatment and intervention outcomes network (ACTION) registry®-Get With The Guidelines (GWTG)®.

Major bleeding is a frequent complication for patients with acute myocardial infarction (AMI) and is associated with significant morbidity and mortality.

Predicting risk of cardiac events among ST-segment elevation myocardial infarction patients with conservatively managed non-infarct-related artery coronary artery disease: An analysis of the Duke Databank for Cardiovascular Disease.

Recent randomized evidence has demonstrated benefit with complete revascularization during the index hospitalization for multivessel coronary artery disease ST-segment elevation myocardial infarction (STEMI) patients; however, this benefit likely depends on the risk of future major adverse cardiovascular events (MACE).

Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis.

The post-thrombotic syndrome frequently develops in patients with proximal deep-vein thrombosis despite treatment with anticoagulant therapy. Pharmacomechanical catheter-directed thrombolysis (hereafter "pharmacomechanical thrombolysis") rapidly removes thrombus and is hypothesized to reduce the risk of the post-thrombotic syndrome.

Drip-and-ship stroke thrombolysis in the emergency department of a healthcare center - a possibility for those fallen ill in rural settings.

Thrombolysis with tissue plasminogen activator is the mainstay in the treatment of acute stroke. Reducing the delay of thrombolysis treatment improves patient prognosis and reduces the incidence of complications. Variable telestroke regimens have improved the availability of stroke thrombolysis, especially in rural settings, where neurologists are not readily available. In the drip-and-ship strategy, stroke thrombolysis is initiated in a peripheral hospital and the patient is then transferred to a tertiary care unit. We report the first case of drip-and-ship stroke thrombolysis in a rural health care center in Northeastern Finland.

High-permeability region size on perfusion CT predicts hemorrhagic transformation after intravenous thrombolysis in stroke.

Blood-brain barrier (BBB) permeability has been proposed as a predictor of hemorrhagic transformation (HT) after tissue plasminogen activator (tPA) administration; however, the reliability of perfusion computed tomography (PCT) permeability imaging for predicting HT is uncertain. We aimed to determine the performance of high-permeability region size on PCT (HPrs-PCT) in predicting HT after intravenous tPA administration in patients with acute stroke.

Considerations in Meta-Analyses to Understand the Value of Intravenous Thrombolysis in Current, Guideline-Based, Endovascular Practice of Stroke Treatment.

Intracerebral Hemorrhage and Outcome After Thrombolysis in Stroke Patients Using Selective Serotonin-Reuptake Inhibitors.

Selective serotonin-reuptake inhibitors (SSRIs) impair platelet function and have been linked to a higher risk of spontaneous intracerebral hemorrhage-an association that may be augmented by oral anticoagulants (OAC). We aimed to assess whether preadmission treatment with SSRIs in patients with acute ischemic stroke is associated with post-thrombolysis symptomatic intracerebral hemorrhage (sICH) and functional outcome.

Comparison of Delay Times Between Symptom Onset of an Acute ST-elevation Myocardial Infarction and Hospital Arrival in Men and Women <65 Years Versus ≥65 Years of Age.: Findings From the Multicenter Munich Examination of Delay in Patients Experiencing Acute Myocardial Infarction (MEDEA) Study.

Early administration of reperfusion therapy in acute ST-elevation myocardial infarctions (STEMI) is crucial to reduce mortality. Although female sex and old age are key factors contributing to an inadequate long prehospital delay time, little is known whether women ≥65 years are a particular risk population. Hence, we studied the interaction of sex and age (<65 years or ≥65 years) and the contribution of chest pain to delay time during STEMI. Bedside interview data were collected in 619 STEMI patients from the Munich Examination of Delay in Patients Experiencing Acute Myocardial Infarction (MEDEA) study. Sex and age group stratification disclosed an excess delay risk for women ≥65 years, accounting for a 2.39 (95% confidence interval (CI) 1.39 to 4.10)-fold higher odds to delay longer than 2 hours compared with all other patient groups including younger women (p ≤0.002). Median delay time was 266 minutes in women ≥65 years and 148 minutes in younger women (p <0.001). Chest pain during STEMI had the lowest frequency both in women (81%) and men ≥65 years (83%) and the highest frequency (95%) in younger women. Experiencing non-chest pain was 2.32-fold (95% CI, 1.20 to 4.46, p <0.05) higher in women ≥65 years than in all other patients. Mediation analysis disclosed that the effect accounted for only 9% of the variance. Age specific educational strategies targeting women ≥65 years at risk are urgently needed. To tailor adequate strategies, more research is required to understand age- and sex driven barriers to timely identification of ischemic symptoms.

Direct Mechanical Intervention Versus Bridging Therapy in Stroke Patients Eligible for Intravenous Thrombolysis: A Pooled Analysis of 2 Registries.

Randomized controlled trials have shown that mechanical thrombectomy (MT) plus best medical treatment improves outcome in stroke patients with large-vessel occlusion in the anterior circulation. Whether direct MT is equally effective as bridging thrombolysis (intravenous thrombolysis plus MT) in intravenous thrombolysis eligible patients remains unclear.

Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

Symptomatic intracranial hemorrhage (sICH) is the most feared complication of intravenous thrombolytic therapy in acute ischemic stroke. Treatment of sICH is based on expert opinion and small case series, with the efficacy of such treatments not well established. This document aims to provide an overview of sICH with a focus on pathophysiology and treatment.

Pregnancy, thrombophilia, and the risk of a first venous thrombosis: systematic review and bayesian meta-analysis.

Objective To provide evidence to support updated guidelines for the management of pregnant women with hereditary thrombophilia in order to reduce the risk of a first venous thromboembolism (VTE) in pregnancy.Design Systematic review and bayesian meta-analysis.Data sources Embase, Medline, Web of Science, Cochrane Library, and Google Scholar from inception through 14 November 2016.Review methods Observational studies that reported on pregnancies without the use of anticoagulants and the outcome of first VTE for women with thrombophilia were eligible for inclusion. VTE was considered established if it was confirmed by objective means, or when the patient had received a full course of a full dose anticoagulant treatment without objective testing. Results 36 studies were included in the meta-analysis. All thrombophilias increased the risk for pregnancy associated VTE (probabilities ≥91%). Regarding absolute risks of pregnancy associated VTE, high risk thrombophilias were antithrombin deficiency (antepartum: 7.3%, 95% credible interval 1.8% to 15.6%; post partum: 11.1%, 3.7% to 21.0%), protein C deficiency (antepartum: 3.2%, 0.6% to 8.2%; post partum: 5.4%, 0.9% to 13.8%), protein S deficiency (antepartum: 0.9%, 0.0% to 3.7%; post partum: 4.2%; 0.7% to 9.4%), and homozygous factor V Leiden (antepartum: 2.8%, 0.0% to 8.6%; post partum: 2.8%, 0.0% to 8.8%). Absolute combined antepartum and postpartum risks for women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutations, or compound heterozygous factor V Leiden and prothrombin G20210A mutations were all below 3%. Conclusions Women with antithrombin, protein C, or protein S deficiency or with homozygous factor V Leiden should be considered for antepartum or postpartum thrombosis prophylaxis, or both. Women with heterozygous factor V Leiden, heterozygous prothrombin G20210A mutation, or compound heterozygous factor V Leiden and prothrombin G20210A mutation should generally not be prescribed thrombosis prophylaxis on the basis of thrombophilia and family history alone. These data should be considered in future guidelines on pregnancy associated VTE risk.

Clinical Policy: Emergency Department Management of Patients Needing Reperfusion Therapy for Acute ST-Segment Elevation Myocardial Infarction.

Therapeutic investigations of novel indoxyl-based indolines: A drug target validation and Structure-Activity Relationship of angiotensin-converting enzyme inhibitors with cardiovascular regulation and thrombolytic potential.

A family of 12 members of Naphthalene-2-ol-indolin-2-one-thiocarbamides (5a-l) with pharmacological potentials of cardiovascular modulator were efficiently synthesized and evaluated. These compounds show inhibitory activity on angiotensin-converting enzyme (ACE), which is a principal constituent of the renin-angiotensin system and causative source for hypertension (HTN) (elevated blood pressure) and congestive heart failure (CHF), a parameter that was tested in this report. Prior to this, to get more insight into the binding mode and inhibition of human ACE C-domain (PDB ID: 2XY9) and N-domain (PDB ID: 3NXQ) compounds 5a-l was docked into the active site of them. The established inhibitory constant (Ki) (range 40-500 nM) and least binding affinities (-18.52 to -30.57 kcal/mol) indicated the therapeutic selectivity of compounds 5a-l towards ACE C-domain inhibition over ACE N-domain. The cytotoxicity effect of most potent compounds among 5a-l were tested in normal breast cells and MCF-7 cell lines. Simultaneously, H2O2 induced antioxidant and DNA damage assessment was executed. Eventually, a thrombolytic activity followed by a human red blood cell (HRBC) membrane stabilization study to ensure the relaxation of blood and stabilization of RBC was executed. Structure-Activity Relationship (SAR) study discloses the potential of 5c, 5h, and 5k as cardiovascular protective therapeutic agents among 5a-l.

The Future of Catheter-Directed Therapy: Data Gaps, Unmet Needs, and Future Trials.

This article will focus on 3 avenues for future research: (1) addressing the lack of short- and long-term clinical outcome research on catheter-directed therapy; (2) determining the safety and efficacy of novel thrombus removal devices; and (3) translating our knowledge of the pathobiology and pathophysiology of pulmonary embolism into novel diagnostic and therapeutic strategies.

Catheter-Directed Therapy for Acute Submassive Pulmonary Embolism: Summary of Current Evidence and Protocols.

Treatment of acute submassive pulmonary embolism (PE) with thrombolytic therapy remains an area of controversy. For patients who fail or who have contraindications to systemic thrombolysis, catheter-directed therapy (CDT) may be offered depending on the patient's condition and the available institutional resources to perform CDT. Although various CDT techniques and protocols exist, the most studied method is low-dose catheter-directed thrombolytic infusion without mechanical thrombectomy. This article reviews current protocols and data on the use of CDT for acute submassive pulmonary embolism.

Techniques and Devices for Catheter-Directed Therapy in Pulmonary Embolism.

The clinical presentation of a patient with acute pulmonary embolism (PE) can be classified into 3 categories: low-risk, submassive (presence of right heart strain), and massive (hemodynamic compromise). Massive PE is associated with high morbidity or mortality and typically treated with systemic intravenous thrombolysis. Over the last 2 decades, however, catheter-directed techniques have become an increasingly popular treatment modality for patients with a contraindication to systemic thrombolysis or without clinical improvement after systemic thrombolysis. Furthermore, endovascular treatment for patients with submassive PE has been of great interest due to the significantly increased mortality associated with right heart strain, and prospective clinical trials have demonstrated catheter-directed thrombolysis to decrease right heart strain earlier than systemic anticoagulation alone. This article describes available devices and endovascular techniques used to treat patients with massive and submassive acute PE.

Advanced Cardiopulmonary Support for Pulmonary Embolism.

Management of high-risk pulmonary embolism (PE) requires an understanding of the pathophysiology of PE, options for rapid clot reduction, critical care interventions, and advanced cardiopulmonary support. PE can lead to rapid respiratory and hemodynamic collapse via a complex sequence of events leading to acute right ventricular failure. Importantly, reduction in pulmonary vascular resistance must be accomplished either by systemic thrombolytics, catheter directed thrombolytics, endovascular clot extraction, or surgical embolectomy. There are important advances in these techniques all of which have a niche role in the cardiopulmonary stabilization of critically ill patient with PE. Critical care support surrounding the above interventions is necessary. Maintenance of systemic perfusion and cardiac output may require careful titration of vasopressors, inotropes, and preload. Extreme caution should be taken with approach to intubation and positive pressure ventilation. A hemodynamically neutral induction with preparations for circulatory collapse should be the goal. Once intubated, the effect of positive pressure on pulmonary vascular resistance and right ventricular hemodynamics is necessary. Veno-arterial extra corporeal membrane oxygenation plays an increasingly important role in the stabilization of the hemodynamically collapsed patient who either has a contraindication to systemic lytics, failed systemic lytics, or requires a bridge to surgical or catheter embolectomy. Veno-arterial extra corporeal membrane oxygenation has also been used alone to stabilize the circulation until hemodynamics normalize on anticoagulation and has also been used in tenuous patient as a safety net for endovascular procedures.

Systemic Thrombolysis for Pulmonary Embolism: Who and How.

Anticoagulation has been shown to improve mortality in acute pulmonary embolism (PE). Initiation of anticoagulation should be considered when PE is strongly suspected and the bleeding risk is perceived to be low, even if acute PE has not yet been proven. Low-risk patients with acute PE are simply continued on anticoagulation. Severely ill patients with high-risk (massive) PE require aggressive therapy, and if the bleeding risk is acceptable, systemic thrombolysis should be considered. However, despite clear evidence that parenteral thrombolytic therapy leads to more rapid clot resolution than anticoagulation alone, the risk of major bleeding including intracranial bleeding is significantly higher when systemic thrombolytic therapy is administered. It has been demonstrated that right ventricular dysfunction, as well as abnormal biomarkers (troponin and brain natriuretic peptide) are associated with increased mortality in acute PE. In spite of this, intermediate-risk (submassive) PE comprises a fairly broad clinical spectrum. For several decades, clinicians and clinical trialists have worked toward a more aggressive, yet safe solution for patients with intermediate-risk PE. Standard-dose thrombolysis, low-dose systemic thrombolysis, and catheter-based therapy which includes a number of devices and techniques, with or without low-dose thrombolytic therapy, have offered potential solutions and this area has continued to evolve. On the basis of heterogeneity within the category of intermediate-risk as well as within the high-risk group of patients, we will focus on the use of systemic thrombolysis in carefully selected high- and intermediate-risk patients. In certain circumstances when the need for aggressive therapy is urgent and the bleeding risk is acceptable, this is an appropriate approach, and often the best one.

Pulmonary Embolism in 2017: How We Got Here and Where Are We Going?

In the 1970s, both the Urokinase Pulmonary Embolism and Urokinase-Streptokinase Pulmonary Embolism trials began the quest to develop thrombolytic therapy for the treatment of acute massive and submassive pulmonary embolism (PE). The goals of these studies were the immediate reduction in clot burden, restoration of hemodynamic stability, and improved survival. Major bleeding became the major barrier for clinicians to employ these therapies. From 1980s to the present time, a number of studies using recombinant tissue-type plasminogen activator for achieving these same above outcomes were completed but major bleeding continued to remain an adoption barrier. Finally, the concept of bringing the thrombolytic agent into the clot has entered the quest for the Holy Grail in the treatment of PE. This article will review all the major trials using peripheral thrombolysis and provide insight into the need for a team approach to pulmonary care (Pulmonary Embolism Response Team), standardization of pulmonary classification, and the need for trials designed for both short- and long-term outcomes using thrombolysis for selected PE populations.

Ischemic Stroke: Advances in Diagnosis and Management.

Acute ischemic stroke carries the risk of morbidity and mortality. Since the advent of intravenous thrombolysis, there have been improvements in stroke care and functional outcomes. Studies of populations once excluded from thrombolysis have begun to elucidate candidates who might benefit and thus should be engaged in the process of shared decision-making. Imaging is evolving to better target the ischemic penumbra salvageable with prompt reperfusion. Availability and use of computed tomography angiography identifies large-vessel occlusions, and new-generation endovascular therapy devices are improving outcomes in these patients. With this progress in stroke treatment, risk stratification tools and shared decision-making are fundamental.

Acute Limb Ischemia: An Emergency Medicine Approach.

Acute limb ischemia is a medical emergency with significant morbidity and mortality. Rapid diagnosis is required because it is a time-sensitive condition. Timely treatment is necessary to restore blood flow to the extremity and prevent complications. The differential diagnosis of acute limb ischemia is broad. Classification of severity of acute limb ischemia is based on clinical variables. A suspicion of acute ischemia based on history and physical examination warrants heparin administration and vascular surgery consultation. The decision for endovascular thrombolysis or standard surgery depends on etiology, duration, and location of vascular occlusion. This review evaluates the diagnostic approach and management for acute limb ischemia.

Deep Venous Thrombosis.

Deep venous thrombosis (DVT) is a frequently encountered condition that is often diagnosed and treated in the outpatient setting. Risk stratification is helpful and recommended in the evaluation of DVT. An evidence-based diagnostic approach is discussed here. Once diagnosed, the mainstay of DVT treatment is anticoagulation. The specific type and duration of anticoagulation depend upon the suspected etiology of the venous thromboembolism, as well as risks of bleeding and other patient comorbidities. Both specific details and a standardized approach to this vast treatment landscape are presented.

Extracranial Cervical Artery Dissections.

Cervical artery dissections (CeAD) include both internal carotid and vertebral artery dissections. They are rare but important causes of stroke, especially in younger patients. CeAD should be considered in patients with strokelike symptoms, a new-onset headache and/or neck pain, and/or other risk factors. Early imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is key to making the diagnosis. Treatment may vary depending on the extent of the dissection, timing of the dissection, and other comorbidities. The overall prognosis is good, but does depend on the initial severity of symptoms.

Veno-Arterial Extracorporeal Membrane Oxygenation with Conventional Anticoagulation Can Be a Best Solution for Shock Due to Massive PE.

While most of pulmonary thromboembolism (PE) cases can be managed by thrombolytic and anticoagulation therapy, massive PE remains a life-threatening disease. Although surgical embolectomy can be a curative therapy for massive PE, peri-operative mortality for hemodynamically collapsed PE is extremely high. We present a case of hemodynamically collapsed massive PE. We avoided either thrombolytic therapy or surgical embolectomy, because the patient had recent cerebral contusion. Therefore, we managed the patient with the combination of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and conventional anticoagulation, which dramatically improved the patient's hemodynamics. In conclusion, the combination of V-A ECMO and conventional anticoagulation may be the preferred first line therapy for the patients with cardiogenic shock following massive PE.

Impact of Postprocedural TIMI Flow on Long-Term Clinical Outcomes in Patients with Acute Myocardial Infarction.

This study aimed to evaluate the clinical prognostic implications of postprocedural Thrombolysis in Myocardial Infarction (TIMI) flow in acute myocardial infarction patients. A total of 2796 ST-elevation myocardial infarction (STEMI) and 1720 non ST-elevation myocardial infarction (NSTEMI) patients treated in 8 hospitals affiliated with the Catholic University of Korea and Chonnam National University Hospital were analyzed. The study populations were divided according to the final TIMI flow. The primary outcome were the major adverse cardiac events (MACE), defined as a composite of cardiac deaths (CD), nonfatal myocardial infarctions (MI), and target lesion revascularization (TLR). Over a median follow-up of 3.3 years (minimum 2 to maximum 5 years), MACE and CD occurred more frequently in STEMI patients with TIMI ≤ 2 group than those with TIMI 3 (MACE: adjusted hazard ratio [aHR], 1.962; 95% confidence interval [CI] 1.513 to 2.546, P < 0.001, CD: aHR, 3.154, CI 2.308 to 4.309, P < 0.001). However, there was no significant difference between the two subgroups in NSTEMI (aHR, 0.932; 95% CI 0.586 to 1.484, P = 0.087). In STEMI patients, good postprocedural TIMI flow after PCI was associated with favorable clinical outcomes. And the effect of poor TIMI flow in STEMI was on death, not the components of MACE. Meanwhile, postprocedural TIMI flow had no effect on long-term outcomes in NSTEMI patients.

Impact of Double Loading Regimen of Clopidogrel on Final Angiographic Results, Incidence of Upper Gastrointestinal Bleeding and Clinical Outcomes in Patients with STEMI Undergoing Primary Coronary Intervention.

This study tested the therapeutic impact of double-loading dose (i.e., 600 mg) versus standard-loading dose (i.e., 300 mg) of clopidogrel on ST-segment-elevation-myocardial-infarction (STEMI) patients undergoing primary-coronary-intervention (PCI).Between January 2005 and December 2013, a total of 1461 STEMI patients undergoing PCI were consecutively enrolled into the study and categorized into group 1 (600 mg/clopidogrel; n = 508) and group 2 (300 mg/clopidogrel; n = 953). We assessed angiographic thrombolysis-in-myocardial-infarction (TIMI) flow in the infarct-related-artery, 30-day mortality and upper-gastrointestinal-bleeding (UGIB) within 30 days as primary-endpoints and later incidents of UGIB as secondary-endpoints.The results showed that the incidences of advanced Killip score (defined as ≥ score 3) upon presentation (23.8% versus 24.6%) and advanced heart failure (defined as ≥ NYHAFc-3) (10.2% versus 10.4%) did not differ between groups 1 and 2 (all P > 0.4). Primary-endpoints, which were final TIM-3 flow (91.3% versus 91.7%) in the infarct-related-artery, incidences of 30-day mortality (5.8% vs. 7.1%), and UGIB ≤ 30 day (7.8% versus 8.9%) did not differ between group 1 and group 2 (all P > 0.33). The secondary-endpoints which were incidences of ≥ 30-day < one-year (5.2% versus 4.7) and > one-year (8.9% versus 10.1%) UGIB did not differ between groups 1 and 2 (all P > 0.45). One-year mortality did not differ between two groups (10.74% versus 12.9%) (P > 0.25). Multiple-stepwise-logistic-regression analysis showed that age and advanced-Killip score were independently predictive of 30-day mortality (all P < 0.001).Double-loading dose of clopidogrel did not confer an additional benefit to the final angiograph results, 30-day/one-year clinical outcomes; and age and advanced Killip-score were powerful predictors of 30-day mortality.

Prevention of Left Ventricular Thrombus Formation and Systemic Embolism After Anterior Myocardial Infarction: A Systematic Literature Review.

Anterior myocardial infarction (MI) with apical dysfunction is associated with an increased risk of left ventricular thrombus (LVT) formation and systemic embolism (SE). However, the role for prophylactic anticoagulation in current practice is a matter of debate.

Effects of ticagrelor versus clopidogrel on platelet function in fibrinolytic-treated STEMI patients undergoing early PCI.

Patients undergoing PCI early after fibrinolytic therapy are at high risk for both thrombotic and bleeding complications. We sought to assess the pharmacodynamic effects of ticagrelor versus clopidogrel in the fibrinolytic-treated STEMI patients undergoing early PCI.