Thrombolytic Administration Research Articles

Standard clinical and imaging-based small vessel disease parameters associated with mild stroke versus non-mild stroke.

Mild stroke has variable outcomes, and there is an ongoing debate regarding whether the administration of thrombolytics improves outcomes in this subgroup of stroke patients. Having a better understanding of the features of mild stroke may help identify patients who are at risk of poor outcomes. The objective of this study is to evaluate the association of clinical and imaging-based small vessel disease features (white matter hyperintensities and cerebral microbleeds) with stroke severity and clinical outcomes in patients with mild stroke. In this retrospective study, mild stroke was defined as a National Institute of Health stroke scale (NIHSS) score <5. Clinical, laboratory and imaging data were compared between patients with mild stroke versus non-mild stroke (NIHSS≥5). Multivariate logistic regression analysis was performed to identify predictors of mild stroke and poor discharge outcome. Among 296 patients included in the study, 131 patients (44%) had mild stroke. On multivariate analysis, patients with mild stroke were three times more likely to have sensory symptoms [odds ratio (OR) = 2.9; 95% confidence interval (CI) = (1.2-6.8)] and four times more likely to have stroke due to small vessel disease (OR = 3.7; 95%CI = 1.4-9.9). Among patients with mild stroke, higher age (OR = 1.1; 95%CI = 1.02-1.1), presence of cerebral microbleed (OR = 4.5; 95%CI = 1.5-13.8), vertigo (OR = 7.3; 95%CI = 1.2-45.1) and weakness (OR = 5.0; 95%CI = 1.2-20.3) as presenting symptoms were more likely to have poor discharge outcome. Sensory symptoms and stroke due to small vessel disease are more common in mild stroke than non-mild stroke. Among patients with mild stroke, presence of cerebral microbleeds on imaging and symptoms of muscle weakness are associated with poor discharge outcome. Larger studies are needed to assess the impact of cerebral microbleed on mild stroke outcomes and risk stratify the benefit of thrombolytics in this group.

Using body cameras to quantify the duration of a Code Stroke and identify workflow issues: a continuous observation workflow time study

Objective‘Code Stroke’ (Code) is used in health services to streamline hyperacute assessment and treatment delivery for patients with ischaemic stroke. However, there are few studies that detail the time spent...

An Echogenic Clot Method for Thrombolysis Monitoring in Thrombotic Stroke Models.

To demonstrate thrombolytic efficacy of a tissue plasminogen activator (tPA)-loaded echogenic liposome (TELIP) formulation in a rabbit thrombotic stroke model (the most relevant animal model for evaluation of directed thrombolytic therapy for ischemic stroke), we sought to develop a means of monitoring thrombus dissolution quantitatively by ultrasound imaging methods. We hypothesized that a gas-free ultrasound contrast agent can be incorporated into blood clots at a concentration that does not affect the tPA-mediated clot dissolution rate, while enabling quantitative assessment of the clot dissolution rate. Clots were formed from a mixture of whole rabbit blood, 1 M calcium chloride, human thrombin and varying amounts of microcrystalline cellulose. Washed clots in tubes were weighed at 30, 60 and 90 minutes after addition of recombinant tPA (rtPA) in porcine plasma (100 μg/ml). Clot echogenicity at each time point was assessed using a Philips HDI 5000 ultrasound system using an L12-5 linear array probe. Recorded Images underwent videodensitometric analysis that converted image reflectivity to mean gray scale values (MGSV). We found that 1.12 mg/ml of microcrystalline cellulose in rabbit blood clots (0.2 ml) provided optimal echogenicity without affecting clot dissolution rates (0.3-0.6 mg/min.) caused by rtPA. The clot dissolution rate measured by videodensitometric analysis of the echogenic clots agreed well with that determined by mass loss measurements (0.28% 0-time value/minute). This method will be important for demonstrating in vivo efficacy with potentially decreased hemorrhagic effects provided by directed tPA vehicles relative to systemic administration of the free thrombolytic.

Controlling NIR-II emitting gold organic/inorganic nanohybrids with tunable morphology and surface PEG density for dynamic visualization of vascular dysfunction.

Luminescent Au nanoparticles (AuNPs) and their organic/inorganic nanohybrids are of interest due to their favorable properties and promising biomedical applications. However, most existing AuNP-based hybrid nanostructures cannot satisfy high efficiency in synthesis, deep tissue penetration, and long blood circulation simultaneously, thus cannot be employed in dynamic monitoring of biomedical applications. In this paper, using Pluronic F127 as a template, we report a robust approach for one-pot synthesis of AuNP-based organic/inorganic nanohybrids (AuNHs) with bright luminescence in the second near-infrared (NIR-II) window, tunable shape, and controllable surface polyethylene glycol (PEG) density. The nanohybrids could be controlled from a necklace-like shape with a dense brush PEG configuration to a spherical structure with a brush PEG coating, which greatly impacts the in vivo biological behavior. Compared to spherical AuNHs, the necklace-shaped AuNHs present a higher quantum yield and longer blood circulation, which are superior to most of the individual AuNPs. With these outstanding features, the necklace-shaped AuNHs could achieve real-time, dynamic visualization of vascular dysfunction, capable of directing the precise administration of thrombolytics (a medicine for the breakdown of blood clots). These findings could provide a powerful guide for designing novel NIR-II nanoprobes toward in vivo dynamic information visualization.

Systemic thrombolytic and ultrasound-assisted catheter-directed thrombolysis for treatment of acute pulmonary embolism: a 7-year, multicenter experience.

Treatment of acute pulmonary embolism (PE) varies based upon risk stratification and ranges from outpatient oral anticoagulation to emergency surgical embolectomy. Patients with high-risk PE can be considered for systemic thrombolytic (ST) based upon guideline recommendations, but intermediate-risk PE does not currently have strong evidence to guide primary reperfusion strategies via thrombolytic administration. Ultrasound-assisted catheter-directed thrombolysis (USAT) is an alternative reperfusion option to ST but is not currently recommended as first line in any key guidelines due to limited available evidence. This retrospective, multicenter, observational study compares 210 patients treated with USAT (n = 105) or ST (n = 105) for acute high- or intermediate-risk PE in three hospitals. Baseline characteristics were significant in that severity of illness was higher in those that received ST, which limited comparisons of outcomes. The primary outcome of major bleeding in patients receiving USAT was 15.2% and 22.9% in those that received ST. Efficacy of reperfusion strategy was observed to be 86.7% of patients in USAT group and 65.7% in ST group. Reperfusion strategies had no difference in in-hospital death, intensive care length of stay, or hospital length of stay. Predefined subgroup analysis found that high-risk PE had higher mortality (14.7%) than intermediate-risk PE (0%) regardless of reperfusion strategy. Upon multivariate analysis, high-risk PE was the only independent risk factor for major bleeding while USAT therapy and intermediate-risk PE were independent predictors of efficacy. Due to the difference in baseline severity of illness, direct comparisons in primary outcomes to each group was not performed. We have described real world usage of both USAT and ST and which patients were likely to receive each therapy at these institutions.

Endovascular Treatment of Large Vessel Occlusion Strokes Caused by Infective Endocarditis: A Systematic Review, Meta-Analysis, and Case Presentation.

Thromboembolic events such as acute ischemic strokes are frequently seen in patients with infective endocarditis (IE). It is generally recommended that the administration of intravenous thrombolytics is avoided in these patients as they might encounter a higher risk of intracranial hemorrhages. In this setting, particularly with a large vessel occlusion (LVO), a mechanical thrombectomy may be an alternative option. In this systematic review and meta-analysis, we aimed to investigate the outcomes and safety of mechanical thrombectomies for LVO stroke patients secondary to IE. A search strategy was developed and we searched PubMed, Scopus, Web of Sciences, and Embase using the words "infective endocarditis", "stroke", and "mechanical thrombectomy". Including 6 studies and 120 patients overall, this study showed that a mechanical thrombectomy might reduce the National Institute of Health Stroke Scale (NIHSS), with a weighted mean difference of -3.06 and a 95% CI of -4.43 to -1.70. The pooled rate of symptomatic intracranial hemorrhages and all-cause mortality were also determined to be 15% (95% CI: 4-47%) and 34% (95% CI:14-61%), respectively. The results of this study showed that a mechanical thrombectomy might be an effective and reasonably safe option for the treatment of LVO strokes caused by IE. However, more large-scale studies are needed to consolidate these results.

559: TENECTEPLASE VERSUS ALTEPLASE FOR THE TREATMENT OF ACUTE ISCHEMIC STROKE

Introduction: Since 1995 alteplase has been the preferred thrombolytic for acute ischemic stroke. Recently, data from prospective trials has shown that treatment with tenecteplase, a variant of alteplase with a longer half-life, results in similar rates of excellent functional outcomes (defined as a modified Rankin Scale (mRS) score of 0 or 1) at 90 days, and similar rates of adverse events, including symptomatic intracranial hemorrhage (sICH). The purpose of this study is to evaluate clinical outcomes after transition from alteplase to primarily tenecteplase for treatment of acute ischemic stroke at our institution. The primary objective was to determine if there was a difference in excellent functional outcome at 90 days in patients treated with tenecteplase versus alteplase for AIS. Methods: This single center, retrospective chart review conducted from March 2019 to July 2021 used a pre-test post-test design. Data from two cohorts was collected: the first cohort included patients treated with alteplase for AIS from March 2019 to March 2020, and the second cohort included patients treated with tenecteplase for AIS from July 2020 to July 2021. We collected baseline demographics and assessed outcomes including favorable mRS at 90 days, major neurologic improvement at 36 hours, time to thrombolytics, and sICH rates. Data collected was adjusted for age and presenting NIH scores. Results: We included 136 patients treated with alteplase and 120 patients treated with tenecteplase. Patients were found to have a significant difference in median NIH score at arrival (8 vs 9, p=0.02), as well as a difference in each stroke severity category (p=0.01). There was no statistically significant difference between groups in age (70 vs 74, p=0.07), comorbidities, mean premorbid mRS (0.6±1.1 vs 0.58±1.19, p=0.886), or number of patients with large vessel occlusion (32% vs 42%, p=0.16). We found no difference in favorable mRS at 90 days between groups (59% vs 61%, p=0.89), major neurologic improvement at 36 hours (57% vs 51%, p=0.48), or sICH rates (2% vs 0%, p=0.48). We saw a decrease in time from arrival to thrombolytic administration (28 vs 22 minutes, p< 0.001). Conclusions: Routine use of tenecteplase was found to have similar efficacy and safety to that of alteplase, and a shorter door-to-needle time.

Impact of Metabolic Syndrome in Patients With Acute Myocardial Infarction After Thrombolytic Therapy

Background: Metabolic syndrome (MetS) comprises a group of conditions that happen together and increase the risk of heart disorders. MetS has known characteristic diagnostic criteria and is diagnosed through physical examination and blood tests. This syndrome is extremely prevalent in patients with acute myocardial infarction. We aimed to determine the prevalence of MetS and its relationship with myocardial infarction and response to treatment in patients suffering from acute myocardial infarction under fibrinolytic treatment. Methods: In this cross-sectional study, 145 patients with acute ST-elevation myocardial infarction (STEMI) were enrolled. They were referred to Bu-Ali Sina Hospital in Qazvin, Iran, between January 2018 and January 2019 and were candidates for thrombolytic therapy. The patients were divided into two groups with and without MetS according to the NCEP ATP III definition (the National Cholesterol Education Program-Adult Treatment Panel III). In each group, the ST resolution of more than 50% in electrocardiogram was evaluated 90 minutes after thrombolytic administration. In addition, angiographic information and left ventricular ejection fraction (LVEF) were compared between the two groups. Results: Overall, the prevalence of MetS was 57.2% in the study population. After treatment, ST-segment resolution of more than 50%, the number of involved coronary vessels, the thrombolysis in myocardial infarction flow grade, mean LVEF, and type of myocardial infarction were similar in both study groups. Conclusion: Our study indicates that MetS does not affect the response rate to thrombolytic treatment.

Speech-language pathologists’ perspectives of dysphagia following reperfusion therapies: An Australian mixed-methods study

Purpose To investigate speech-language pathologists’ (SLPs) perceptions and clinical experiences of dysphagia management following reperfusion therapies. Method A multi-staged mixed approach involving a two-phase cross-sectional design was used. Data generated during phase 1 (a purpose-built, online survey) guided the development of phase 2 (semi-structured interviews). Sixty-two SLPs participated in phase 1 and six SLPs participated in phase 2. Result SLPs in both phases reported perceived changes in dysphagia presentation according to the success of reperfusion therapy administered and had concerns regarding worsened dysphagia following unsuccessful procedures. Fluctuations in dysphagia were more frequently reported in the acute stage post-stroke. SLPs reported increased workload demands due to increased interhospital transfers between ECR/thrombolysis centres and referring facilities. The optimal timing for swallowing screening and assessment was not identified, with initial SLP involvement ranging from during the administration of thrombolysis to up to 24 hours post-reperfusion therapy. Conclusion Preliminary evidence suggests that SLPs perceive that the presentation of post-stroke dysphagia is changing, with increasing fluctuations and complexities in the acute stage of post-stroke care, within the context of increasing use of reperfusion therapies. There is a critical need for research investigating the trajectory of dysphagia in the acute stage to inform dysphagia management within this patient population.

One-year recurrence of stroke and death in Lebanese survivors of first-ever stroke: Time-to-Event analysis.

To date, despite the application of secondary prevention worldwide, first-ever stroke survivors remain at imminent risk of stroke recurrence and death in the short and long term. The present study aimed to assess the cumulative risk rates and identify baseline differences and stroke characteristics of Lebanese survivors. A prospective longitudinal study was conducted among survivors ≥18 years old who were followed-up for 15 months through a face-to-face interview. Kaplan-Meier method was used to calculate the cumulative rates of stroke mortality and recurrence. Cox-regression univariate and multivariable analyses were performed to identify the predictors of both outcomes. Among 150 subjects (mean age 74 ± 12 years; 58.7% men vs. 44.3% women; 95.3% with ischemic stroke vs. 4.3% with intracerebral hemorrhage), high cumulative risk rates of stroke recurrence (25%) and death (21%) were highlighted, especially in the acute phase. Survival rates were lesser in patients with stroke recurrence compared to those without recurrence (Log rank test p < 0.001). Older age was the main predictor for both outcomes (p < 0.02). Large artery atherosclerosis was predominant in patients with stroke recurrence and death compared to small vessel occlusion (p < 0.02). Higher mental component summary scores of quality of life were inversely associated with stroke recurrence (p < 0.01). Lebanese survivors exhibited the highest percentages of depression and anxiety; elevated Hospital Anxiety and Depression Scale (HADS) scores were seen in those with stroke recurrence and those who died (≥80% with mean HADS scores ≥8). Lower Mini-Mental State Examination scores at the acute phase increased the risk of both outcomes by 10% (p < 0.03). Three out of 13 mortalities (23.1%) were presented with early epileptic seizures (p = 0.012). High educational level was the protective factor against stroke recurrence (p = 0.019). Administration of intravenous thrombolysis decreased the risk of both outcomes by 10% (p > 0.05). Higher rates of stroke recurrence and death were observed in the first year following a stroke in Lebanon. Various factors were identified as significant determinants. Thus, health care providers and officials in Lebanon can use these findings to implement effective preventive strategies to best address the management of these factors to reduce the stroke burden and improve the short and long-term prognosis of stroke survivors.

Impact of clinical profile at admission on the outcomes in patients hospitalized for acute pulmonary embolism: data from the IPER Registry.

Acute pulmonary embolism (PE) is characterized by a large heterogeneity of clinical presentation and disease course. We investigate whether different symptom PE phenotypes in hemodynamically stable PE could be associated with 30-day mortality risk. Hemodynamically stable patients from the multicentre, prospective Italian Pulmonary Embolism Registry (IPER) (September 2006-August 2010) presenting the most common four clinical phenotypes (< 24h onset dyspnoea, chest pain, pleuritic pain and phlebitis) at admission were included and compared to those who were asymptomatic at admission. Overall, 1365 (mean age 68.7 ± 15.3 years, 609 males) were evaluated. Recent onset dyspnoea (< 24h), chest pain, pleuritic pain and phlebitis were observed in 28.4%, 19.7%, 12.9% and 25.2%, respectively while asymptomatic patients represented the remaining 13.6% of cases. PE presenting with recent dyspnoea onset and chest pain had a lower 30-day overall survival (log-rank p = 0.01 and p < 0.001, respectively). By contrast, there were no significant differences when comparing patients with pleuritic pain or phlebitis (log-rank p = 0.2). Similar findings were confirmed at the Cox multivariate regression analysis which indicated a higher mortality risk in patients with chest pain [HR 3.21, 95% CI 2.16-4.78, p < 0.001] or recent dyspnoea [HR 2.12, 95% CI 1.22-3.87, p = 0.002] independent of age, heart rate, presence of right ventricular dysfunction, positive cardiac troponin and administration of systemic thrombolysis. Hemodynamically stable PE patients presenting with chest pain or recent onset dyspnoea had a lower 30-day survival compared to those asymptomatic or presenting pleuritic or phlebitis pain.Trial registryClinicalTrials.gov; No: NCT01604538).

Clinical Outcomes of Extracranial Carotid Artery-Related Stroke Eligible for Mechanical Reperfusion on Top of Per-Guidelines Thrombolytic Therapy: Analysis from a 6-Month Consecutive Patient Sample in 2 Centers.

BACKGROUND Systemic intravenous thrombolysis and mechanical thrombectomy (MT) are guideline-recommended reperfusion therapies in large-vessel-occlusion ischemic stroke. However, for acute ischemic stroke of extracranial carotid artery origin (AIS-CA) there have been no specific trials, resulting in a data gap. MATERIAL AND METHODS We evaluated referral/treatment pathways, serial imaging, and neurologic 90-day outcomes in consecutive patients, presenting in a real-life series in 2 stroke centers over a period of 6 months, with AIS-CA eligible for emergency mechanical reperfusion (EMR) on top of thrombolysis as per guideline criteria. RESULTS Of 30 EMR-eligible patients (33.3% in-window for thrombolysis and thrombolysed, 73.3% male, age 39-87 years, median Alberta Stroke Program Early Computed Tomography Score (ASPECTS) 10, pre-stroke mRS 0-1 in all, tandem lesions 26.7%), 20 (66.7%) were EMR-referred (60% - endovascular, 6.7% - surgery referrals). Only 40% received EMR, nearly exclusively in stroke centers with carotid artery stenting (CAS) expertise (100% eligible patient acceptance rate, 100% treatment delivery involving CAS±MT with culprit lesion sequestration using micronet-covered stents). The emergency surgery rate was 0%. Baseline clinical and imaging characteristics did not differ between EMR-treated and EMR-untreated patients. Ninety-day neurologic status was profoundly better in EMR-treated patients: mRS 0-2 (91.7% vs 0%; P<0.001); mRS 3-5 (8.3% vs 88.9%; P<0.001), mRS 6 (0% vs 11.1%; P<0.001). CONCLUSIONS In a real-life AIS-CA setting, the referral rate of EMR-eligible patients for EMR was low, and the treatment rate was even lower. AIS-CA revascularization was delivered predominantly in stroke thrombectomy-capable cardioangiology centers, resulting in overwhelmingly superior patient outcome. Large vessel occlusion stroke referral and management pathways should involve centers with proximal-protected CAS expertise. AIS-CA, irrespective of any thrombolysis administration, is a hyperacute cerebral emergency and EMR-eligible patients should be immediately referred for mechanical reperfusion.

Has low-dose intracoronary thrombolysis gained ground in primary percutaneous intervention?

Reducing thrombus burden would improve patient's outcomes. Low-dose intracoronary thrombolytic agent administration has been considered to improve myocardial microcirculation, cardiac function, and major adverse cardiovascular events in patients presenting with ST-segment elevation myocardial infarction and high thrombus burden. This paper discusses published meta-analyses on intracoronary thrombolysis in primary percutaneous intervention.

Clinical Case 06—A fatal dance: a case report of a pulmonary embolism with mobile right ventricular thrombus

Abstract Presentation We report a case of a 44-year-old woman with past medical history of dyslipidemia under atorvastatin, overweight and depression, that presented to the emergency department with a 1-month history of dyspnea. On physical examination, blood pressure was within normal range, however she was hypoxemic, needing oxygen via nasal cannula, and tachycardic. Pulmonary auscultation revealed basal crackles. Blood workup showed discrete leukocytosis, increased C-reactive protein, mild hypertransaminasemia and increased troponin and NT-proBNP levels. An EKG revealed sinus tachycardia with 123 beats per minute. A D-shaped left ventricle, an enlarged right ventricle and right heart mobile thrombus were observed in a transthoracic echocardiogram. Diagnosis Scoring 2 points on simplified Wells’ Score and with a visible mobile right ventricular thrombus, pulmonary embolism was suspected and further confirmed by computed tomographic pulmonary angiography. Management: In the absence of hemodynamic instability this case fulfils criteria for intermediate-high risk pulmonary embolism. Therefore, anticoagulation with enoxaparin was started under strict electrocardiographic monitoring. Unfortunately, a day later the patient had a sudden cardiac arrest in asystole, with no recuperation after prolonged advanced life support and administration of rescue thrombolysis (alteplase 50mg). Learning points

Determinants of Exclusion from Treatment with Alteplase in Acute Ischemic Stroke at the Largest Tertiary Center in Lebanon

Objectives: Thrombolysis remains underutilized for Acute Ischemic Stroke (AIS) in healthcare systems in low- and middle-income countries. We aimed to investigate the factors associated with utilization of intravenous thrombolysis in an academic medical center in Lebanon. Materials and Methods: This is a retrospective, cross-sectional, singlecentered, chart review-based study of AIS patients presenting to the American University of Beirut Medical Center (AUBMC) between January 2015 and October 2019. Included patients were older than 18 years and presented to the Emergency Department (ED) within 48 hours from symptom onset. Patient, disease, and health system response characteristics were collected and those eligible for and those who received thrombolysis within 4.5 hours onset by guidelines criteria were identified by chart review. Descriptive statistics, bivariate and multivariate analyses were performed for association with thrombolysis administration. Results: Out of the 373 AIS patients, 17.4% were candidate for rTPA and of those, 38.5% did not receive treatment. Patients who were candidate for IV alteplase had a higher NIHSS (OR 1.22 [1.14-1.31], p&lt;0.0001), total or partial anterior circulation stroke (OR 3.58 [1.49-8.6, p=0.004) as compared to posterior or lacunar strokes and a shorter duration since symptom onset (OR 0.14 [0.07- 0.27, p&lt;0.0001). The multivariate analysis showed that thrombolysis among eligible patients associated with younger age (OR 1.05 [1.01-1.10], p=0.029), a higher NIHSS (OR 1.12 [1.01-1.25], p=0.041), and stroke code activation (OR 2.81 [1.16-6.81], P=0.022). Conclusion: A good proportion of eligible AIS patients did not receive thrombolysis. To increase thrombolysis use in low- and middle-income countries, more consistent stroke code activation and education on age and stroke severity in eligibility are needed.

Start, Stop, Continue? The Benefit of Overlapping Intravenous Thrombolysis and Mechanical Thrombectomy

ObjectiveHere we compare the procedural and clinical outcome of patients undergoing thrombectomy with running thrombolysis to matched controls with completed intravenous therapy and an only marginally overlapping activity.MethodsPatients from 25 sites in Germany were included, who presented with an acute ischemic stroke. Patients’ baseline characteristics (including ASPECTS, NIHSS and mRS), grade of reperfusion, and functional outcome 24 h and at day 90 after intervention were extracted from the German Stroke Registry (n = 2566). In a case-control design we stepwise matched the groups due to age, sex and time to groin puncture and time to flow restoration.ResultsIn the initial cohort (overlap group n = 864, control group n = 1702) reperfusion status (median TICI in overlap group vs. control group: 3 vs. 2b), NIHSS after 24 h, early neurological improvement parameters, mRS at 24 h and at day 90 were significantly better in the overlap group (p < 0.001) with a similar risk of bleeding (2.9% vs. 2.4%) and death (18% vs. 22%). After adjustment mRS at day 90 still showed a trend for lower disability scores in the overlap group (3 IQR 1-5 vs. 3 IQR 1-6, p = 0.09). While comparable bleeding risk could be maintained (4% in both groups), there were significantly more deaths in the control group (18% vs. 30%, p = 0.006).ConclusionThe presented results support the approach of continuing and completing a simultaneous administration of intravenous thrombolysis during mechanical thrombectomy procedures.

Low-Dose Thrombolysis in an Intermediate High-Risk Submassive Pulmonary Embolism With Right Atrial Thrombus: A Case Report

BACKGROUND: Venous thromboembolism, encompassing pulmonary embolism (PE) and deep vein thrombosis (DVT), is the third most common acute cardiovascular syndrome. It requires prompt diagnosis and risk-based treatment strategies. CASE: A 47-year-old male, 30-pack-year smoker who recently underwent open reduction and internal fixation of the right femur presented with dyspnea. There was no hemodynamic instability. Twelve-lead electrocardiogram showed sinus rhythm with incomplete right bundle-branch block, and troponin was elevated. Chest x-ray showed dilated right descending pulmonary artery. Two-dimensional echocardiogram revealed right atrial thrombus with right ventricular dysfunction. Computed tomography of the pulmonary artery confirmed massive PE with infarct on the posterobasal segment of the right lower lobe. Venous duplex scan of the lower extremities showed an acute DVT of the right femoral vein, popliteal vein, and peroneal vein. Anticoagulation was started. With a dilemma of a recent surgery in an intermediate high-risk submassive PE, options other than guideline-recommended systemic thrombolysis were considered. A multidisciplinary consensus recommended the administration of low-dose thrombolysis, which later resulted to clinical improvement. CONCLUSION: This is the first documented local case of successful resolution of a right atrial thrombus with pulmonary thrombus and DVT using low-dose thrombolysis, without complications of bleeding, in a patient with contraindications to thrombolysis. With more clinical experience and studies of low-dose recombinant tissue plasminogen activator in this special population, it can offer a promising treatment option. KEYWORDS: pulmonary embolism, submassive, low-dose systemic thrombolysis, contraindication for thrombolysis, alteplase, tPA, right atrial thrombus

OPTIMAL REPERFUSION STRATEGY IN ACUTE HIGH-RISK PULMONARY EMBOLISM REQUIRING EXTRACORPOREAL MEMBRANE OXYGENATION SUPPORT: A SYSTEMATIC REVIEW AND META-ANALYSIS

TYPE: Late Breaking Abstract TOPIC: Pulmonary Vascular Disease PURPOSE: Optimal pulmonary revascularization strategy in acute high-risk pulmonary embolism (PE) requiring implantation of extracorporeal membrane oxygenation (ECMO) remains controversial. METHODS: We conducted a systematic review and meta-analysis of available evidence comparing mechanical embolectomy and other strategies, including systemic or catheter-directed thrombolysis, or ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes. RESULTS: We identified 835 studies;17 were included, comprising 353 PE ECMO-treated patients. Overall, 30.8% had mechanical pulmonary reperfusion, (of whom 89.9% surgical embolectomy), while 69.1% received other strategies. Mortality rate was 23.0% in the mechanical reperfusion group and 43.1% in the other strategy group. The pooled OR for mortality with mechanical reperfusion was 0.46 (95%CI, 0.213-0.997; I2 = 28.3%) versus other reperfusion strategies; and 0.37 (95% CI, 0.18-0.78; p = 0.009; I 2 = 14.8%) for any surgical embolectomy vs thrombolysis. The bleeding rate in ECMO patients was 29.1% in the mechanical reperfusion group and 26.0% in the other reperfusion group (OR, 1.09; 95% CI, 0.46-2.54; I2, 0.0%) among 10 eligible studies with available bleeding data. Meta-regression did not identify any relationship between the covariates “more than one pulmonary reperfusion therapy” and “ECMO implantation before pulmonary reperfusion therapy”, and associated outcomes. CONCLUSIONS: The results of this meta-analysis and meta-regression suggest that mechanical reperfusion, notably surgical embolectomy, yields favorable results regardless of the timing of ECMO implantation in the reperfusion timeline, and independent of thrombolysis administration. CLINICAL IMPLICATIONS: Mechanical pulmonary reperfusion, especially surgical embolectomy, seems to be more effective than other strategies, especially thrombolysis, for mitigating mortality risk, at similar bleeding risk. DISCLOSURE: Grants from BMS/Pfizer, BSC, Amgen, Bayer, Janssen, Portola (GP); Honoraria from Getinge, Drager, Fresenius (MS); Honoraria from Abbott, BMS-Pfizer, Bayer, Edwards Lifesciences, Terumo (NM); Travel support from Daiichi Sankyo, Pfizer (ISC) KEYWORD: pulmonary embolism

P280 USE OF SYSTEMIC THROMBOLYSIS IN HEMODYNAMICALLY UNSTABLE PULMONARY EMBOLISM PATIENTS WITH AND WITHOUT CARDIAC ARREST: DATA FROM THE IPER REGISTRY

Abstract Background Systemic thrombolysis (ST) remains the treatment of choice in haemodynamically unstable patients with acute pulmonary embolism (PE). However, it remains frequently underused in clinical practice. The purpose of the study is to evaluate the use of ST in hemodynamically unstable PE patients with aand without acute cardiac arrest using the IPER registry. Materials and Methods IPER is a multicentre, national, prospective, web–based registry based on 47 Italian hospitals. In this study, the population was divided into two groups: patients with (ACC) and without (No ACC) cardio–circulatory arrest at admission. Results Of 1716 patients enrolled between September 2006 and August 2010, 201 (11.7%) [mean age 74 ± 14 years 127 females] were defined as high risk (i.e. haemodynamically unstable). Of these 59 (29.4%, mean age 76.4 ± 13.3 years, 40 females) were admitted with ACC while the remaining 142 (70.6, mean age 73.5 ± 13.7 years, 87 females) without. No differences were observed for venous thromboembolism risk factors, such as immobilization for more than three days, trauma, surgery within the previous 4 weeks, previous venous thromboembolism, history of heart failure, cancer and ischemic heart disease, among the two gropus. Mortality from all causes (62.7% vs 19.0, p &amp;lt; 0.001) and for acute PE (55.9% vs 9.9%, p &amp;lt; 0.001) was higher in ACC patients. Thrombolysis was administered in 82 (40.7%) of haemodynamically unstable patients and more frequently in ACC subjects (55.9% VSA 34.5%, p = 0.005) (Figure 1, panel A). The administration of systemic thrombolysis increased with aging in the No ACC group but showed a significant reduction in over–octogenarian patients (Figure 1, panel B). Major bleeding complications following reperfusive treatment were observed in 8 patients (3.9%); among these, intracranial hemorrhage was registered in 2.4% of cases. Conclusions Although systemic thrombolysis remains the first–line treatment in patients with hemodynamically unstable acute PE and is capable of improving both the mortality and morbidity, it continues to be underused in daily clinical practice, often for fear of major bleeding complications.

INTRAVENOUS THROMBOLYTIC THERAPY FOR ACUTE NONARTERITIC CENTRAL RETINAL ARTERY OCCLUSION. A REVIEW.

Central retinal artery occlusion (CRAO) is a form of acute ischemic stroke. It is a critical condition that often leads to severe visual loss or blindness and can be a harbinger of further cerebrovascular events. Due to the lack of scientific data, there are no effective evidence-based forms of therapy for this condition. None of the conservative therapies have proven effective. The results of some previously published studies suggest a benefit of intravenous thrombolytic therapy in the same regimen as in the treatment of ischemic stroke. This work aims to present an overview of published clinical studies focused on the use of intravenous thrombolysis for CRAO, evaluate its efficacy and safety, and propose an optimal diagnostic and therapeutic algorithm for acute management of CRAO. Summary statistics of patient data from relevant studies indicate that a significant visual acuity improvement was achieved by a total of 45 % of patients receiving alteplase within 4.5 hours of symptoms onset. The occurrence of adverse events in this time window was not significant. Intravenous thrombolytic therapy in CRAO thus appears to be effective and safe. However, we still lack data from adequate prospective randomized controlled trials to confirm this conclusion. To date, two randomized trials are being conducted. The intravenous thrombolysis administration, patient monitoring, etiologic workup, and setting of effective secondary prevention should be ensured at the centre of highly specialized cerebrovascular care. Urgent transport of the CRAO patient to the nearest centre is essential.