Discussion on the causes of thrombolysis failure in a patient with STEMI: a case report.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) has emerged as an increasingly diagnosed cause of ST-segment elevation myocardial infarction (STEMI), which is easily missed or delayed. The effective use of coronary angiography (CAG) and advanced intracoronary imaging examinations in STEMI patients has led to increased detection of SCAD. CASE PRESENTATION: A 59-year-old woman with acute angina pectoris was diagnosed with STEMI detected by electrocardiography combined with measurement of myocardial enzymes. Due to the ongoing pandemic of coronavirus disease 2019 (COVID-19) in Wuhan, she was first given thrombolytic therapy after excluding contraindications according to the requirements of the current consensus statement; however, subsequently, both the symptoms of ongoing chest pain and the electrocardiographic results indicated the failure of thrombolytic therapy, so the intervention team administered rescue percutaneous coronary intervention treatment under third-grade protection. CAG confirmed total occlusion in the distal left anterior descending (LAD) artery, with thrombolysis in myocardial infarction (TIMI) 0 flow, whereas the left circumflex and right coronary arteries appeared normal, with TIMI 3 flow. Intravenous ultrasound (IVUS) was further performed to investigate the causes of occlusion, which verified the absence of atherosclerosis but detected SCAD with intramural haematoma. During the operation, the guidewire reached the distal end of the LAD artery smoothly, the balloon was dilated slightly, and the reflow of TIMI blood could be seen by repeated CAG. During the follow-up period of one and a half years, the patient complained of occasional, slight chest tightness. The repeated CAG showed that the spontaneous dissection in the LAD artery had healed well, with TIMI 3 flow. The repeated IVUS confirmed that the SCAD and intramural haematoma had been mostly resorbed and repaired. CONCLUSION: This was a case of failed STEMI thrombolysis in our hospital during the outbreak of COVID-19. This case indicates that doctors need to consider the cause of the disease when treating STEMI patients, especially patients without traditional cardiovascular risk factors. Moreover, CAG and intracoronary imaging examinations should be actively performed to identify the aetiology and improve the treatment success rate.

Recombinant tissue plasminogen activator (rTPA) management for first onset acute ischemic stroke with covid -19 and non-covid -19 patients.

OBJECTIVES: Cerebrovascular stroke (CVS) is one of the well-known complications of coronavirus-2019 (Covid-19), but less is known about the outcome and safety of thrombolytic therapy in these patients. In this study we compare the efficacy and safety of Tissue plasminogen activator (rTPA) in acute ischemic stroke (AIS) patients with or without Covid-19 infection. MATERIALS AND METHODS: A comparative prospective study in which all patients who presented with AIS and eligible for rTPA were recruited from the emergency department and classified into 2 groups (AIS with Covid-19 infection and AIS without Covid-19 as controls). Demographic data, symptoms of Covid-19, clinical examination, neuroimaging, and laboratory investigations were obtained in each patient. National Institute of Health Stroke Scale (NIHSS) and the Modified Rankin Scale (mRS) were assessed before, immediately after rTPA, and 3 months later. RESULTS: There were 22 patients in the COVID-19 group and 25 control patients. Those with COVID-19 were more likely to have a history of smoking and Diabetes Mellitus than controls. On admission, motor symptoms were more severe in patients with COVID-19. COVID-19 patients were more likely to have symptomatic intra-cerebral hemorrhage and radiological hemorrhagic transformation than controls. Onset to door time (ODT) and onset to successful reperfusion time were significantly longer in Covid-19 patients than controls. Clinical improvement and frequency of re-occlusion and recurrent ischemic stroke at 3 months follow-up did not differ between groups, although there was higher number of deaths (27.3%) in the Covid-19 group than controls (16%). CONCLUSIONS: Using rTPA is safe and effective in patients with AIS with or without COVID-19 infection despite the high frequency of hemorrhagic transformation and high number of deaths.

COVID-19 and Stroke Trends in A Tertiary Care Center from South India -Our Monsoon Experience.

Introduction: The unprecedented challenges during the COVID pandemic and the subsequent lockdown had resulted in a delay in treatment metrics for acute stroke. There is a rising concern that COVID-19 co-infection can adversely affect stroke outcome. We aim to investigate the impact of COVID-19 in the management of stroke patients. We also compared the differences in stroke manifestations, etiological pattern, treatment course, and outcome of acute stroke patients in COVID-19 confirmed cases. Methodology: A single-center retrospective study was done at the Stroke Unit, Government Medical College, Thiruvananthapuram. Consecutive patients of acute stroke confirmed by imaging, presenting within 24 hours of the onset of symptoms in May to July 2020 and May to July 2019, were included. The primary data variables included baseline demographics, risk factors, admission NIHSS, stroke timings, thrombolysis rate, TOAST etiology, mRS at discharge, and in-hospital mortality. Results: Strokes with higher NIHSS, arrival blood sugar and blood pressure, and delays in door-to-CT and door-to-needle time were more during the pandemic. Intravenous thrombolysis was less and mortality was higher in COVID-19 strokes during the pandemic. COVID-19-positive stroke patients had more hemorrhagic strokes, more severe strokes with low CT ASPECTS, more hemorrhagic transformation, high in-hospital mortality, and poor functional outcome at discharge and 3 months. Conclusion: Our study was a hypothesis-generating study with a limited number of patients. This study has reconfirmed the higher severity of the stroke, with a higher mRS score and mortality during the pandemic, especially among COVID-19-positive stroke patients.

Prognostic significance of age in patients with acute ischaemic stroke treated with intravenous thrombolysis.

AIM OF THE STUDY: To assess the influence of age on long-term functional outcome in patients with acute ischaemic stroke (AIS) treated with intravenous thrombolysis (IVT). MATERIAL AND METHODS: We performed retrospective analysis of 362 AIS patients treated with IVT or IVT and subsequent mechanical thrombectomy in the University Hospital in Krakow, Poland. Patients were categorised into four subgroups by age: (I) below the age of 60, (II) 60 to 69, (III) 70 to 79, and (IV) 80 or more. The outcomes were assessed with modified Rankin scale (mRS) 90 days after stroke onset, and defined as favourable (mRS 0-2), poor (mRS 3-5), or death (mRS = 6). RESULTS: Patients aged 80 or more compared to those below 60 were more often women (72.64% vs. 26.76%, < 0.001), more often suffered from hypertension (94.34% vs. 60.56%, p < 0.001), ischaemic heart disease (27.36% vs. 8.45%, p = 0.002), atrial fibrillation (49.06% vs. 5.63%, p < 0.001), and premorbid disability (pre-stroke mRS ≥ 1: 17.92% vs. 1.41%, p < 0.001), less often were active smokers (0% vs. 27.14%, p < 0.001), more often had cardioembolic aetiology (50.00% vs. 16.90%, p < 0.001), and less often other stroke aetiology (1.89% vs. 15.49%, < 0.008), had shorter time from stroke onset to IVT (125 [93-180] vs. 140 [110-186] min, p < 0.008), less often underwent mechanical thrombectomy (18.87% vs. 46.48%, p < 0.001), had higher CRP levels (10.3 [3.2-39.8] vs. 4.3 [2.1-9.6] mg/L, p = 0.003), higher maximal systolic blood pressure within 24 hours after IVT (153 [140-170] vs. 138 [120-145] mmHg, p < 0.001), and higher creatinine concentration (88 [68-108] vs. 77 [67-87] µmol/l, p = 0.004), less often had a favourable outcome (48.04% vs. 85.51%, odds ratio [OR] 0.16, 95%CI: 0.07-0.34, p < 0.001), and had a greater risk of death (26.47% vs. 5.80%, OR 5.85, 95%CI: 1.95-17.59, p < 0.001) within three months of stroke onset. Multivariable logistic regression analysis showed that the independent predictors of worse outcome in patients aged 80 or more were NIHSS score after IVT (OR 0.64, 95%CI: 0.53-0.78, p < 0.001), pre-stroke mRS score ≥ 1 (OR 0.10, 95%CI: 0.02-0.61, p = 0.012), and CRP levels (OR 0.96, 95%CI: 0.93-0.99, p = 0.007). CONCLUSIONS: AIS patients treated with reperfusion therapy and aged 80 or more have around a six times higher risk of an unfavourable outcome or death within three months of stroke onset compared to those aged below 60. Higher NIHSS score after IVT, any signs of disability before stroke as measured with mRS, and higher CRP levels are independent risk factors for worse prognosis in the elderly.

Diagnosis of coronary artery rethrombosis after effective systemic thrombolytic therapy in patients with ST-segment elevation myocardial infarction.

The aim of the study was to evaluate the diagnostic significance of ST-segment re-elevation episodes registered with telemetric ECG monitoring in patients with ST-segment elevation myocardial infarction (STEMI) treated with thrombolytic therapy (TLT). The study included 117 patients with STEMI following effective TLT. The elective coronary angiography followed by percutaneous coronary interventions was performed in the interval from 3 to 24 hours after a successful systemic TLT. Before and after cardiac catheterization, the telemetric ECG monitoring was performed using AstroCard Telemetry system (Meditec, Russia). During the study, two groups of patients were formed. Group 1 included 85 patients (72.6%) without new ST-segment deviations on telemetry. 77 patients (90.6%) had no recurrent coronary artery thrombosis at angiography. Eight patients (9.4%) from group 1 were diagnosed with thrombosis of the infarct-related coronary artery. Group 2 included 32 patients (27.4%) who underwent TLT and then had ST-segment re-elevation episodes of 1 mV or more in the infarct-related leads, lasting for at least 1 minute. In group 2, in 27 of 32 patients (84.4%), thrombosis of the infarct-related coronary artery was confirmed (p<0.01 compared with group 1). In 71.9% cases, the recurrent ischemic episodes were asymptomatic ('painless myocardial ischemia') (p<0.01). Thus, in patients with STEMI and successful TLT, re-elevation of ST-segment during remote ECG monitoring is strongly related to angiographically documented coronary artery thrombotic reocclusion. The absence of chest pain during recurrent myocardial ischemia requires continuous ECG telemetry to select patients for the rescue percutaneous coronary interventions at an earlier stage.

The Outcome of Catheter-Directed Thrombolysis in COVID-19-Associated Deep Vein Thrombosis.

IntroductionPublished evidence of venous thrombotic complications of COVID-19 is lacking from India. This case series consists of twenty-nine adult patients who were COVID -19 positive and treated for Deep Vein Thrombosis (DVT) during the second wave of the COVID-19 pandemic, in India. The study was aimed at analyzing patient demographics of patients with DVT and the outcome of Catheter-Directed Thrombolysis (CDT) in COVID positive patients. Material and Methods: Patients who developed DVT while or after being COVID positive were managed between February and April 2021 at the institution of the first two authors and were included in this retrospective study. Demographic, clinical data, laboratory data, and treatment given were analyzed. All patients were followed up for 3 months with a Villalta score. Results: There were a total of 29 patients (12 male and 17 female) included in the study with a mean age of 47 ± 17 years. The average time of presentation from being COVID positive was 17.8 ± 3.6 days and one patient developed DVT after becoming Covid negative. All but one patient had lower limb involvement, with 42.8% having proximal and 57.2% distal DVT. All patients with Iliofemoral and two with Femoropopliteal DVT were treated with catheter-di thrombolysis and the other 15 patients were managed with anticoagulation alone. No re-thrombosis was observed in the thrombolysis group. Overall average Villalta score at 3 months was 10.7 ± 2.1 with a score of 10.58 ± 2.1 in the anticoagulation-only group and 10.85 ± 2.3 in the CDT group. Conclusion: COVID-19 seems to be an additional risk factor in the development of DVT. The outcome of such patients, treated by thrombolysis appears to be similar to non-COVID patients. In this, observational experience of the authors suggests that CDT could be offered to COVID positive patients with symptomatic Iliofemoral DVT with good outcomes and an acceptable post-intervention Villalta score.

Nebulization of Low-Dose S-Nitrosoglutathione in Diabetic Stroke Enhances Benefits of Reperfusion and Prevents Post-Thrombolysis Hemorrhage.

The COVID-19 pandemic has escalated the occurrence of hypoxia including thrombotic stroke worldwide, for which nitric oxide (NO) therapy seems very promising and translatable. Therefore, various modes/routes of NO-delivery are now being tested in different clinical trials for safer, faster, and more effective interventions against ischemic insults. Intravenous (IV) infusion of S-Nitrosoglutathione (GSNO), the major endogenous molecular pool of NO, has been reported to protect against mechanical cerebral ischemia-reperfusion (IR); however, it has been never tested in any kind of "clinically" relevant thromboembolic stroke models with or without comorbidities and in combination with the thrombolytic reperfusion therapy. Moreover, "IV-effects" of higher dose of GSNO following IR-injury have been contradicted to augment stroke injury. Herein, we tested the hypothesis that nebulization of low-dose GSNO will not alter blood pressure (BP) and will mitigate stroke injury in diabetic mice via enhanced cerebral blood flow (CBF) and brain tissue oxygenation (PbtO2). GSNO-nebulization (200 µg/kgbwt) did not alter BP, but augmented the restoration of CBF, improved behavioral outcomes and reduced stroke injury. Moreover, GSNO-nebulization increased early reoxygenation of brain tissue/PbtO2 as measured at 6.5 h post-stroke following thrombolytic reperfusion, and enervated unwanted effects of late thrombolysis in diabetic stroke. We conclude that the GSNO-nebulization is safe and effective for enhancing collateral microvascular perfusion in the early hours following stroke. Hence, nebulized-GSNO therapy has the potential to be developed and translated into an affordable field therapy against ischemic events including strokes, particularly in developing countries with limited healthcare infrastructure.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): A case series.

A prothrombotic coagulopathy is commonly found in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS). A unique feature of COVID-19 respiratory failure is a relatively preserved lung compliance and high Alveolar-arterial oxygen gradient, with pathology reports consistently demonstrating diffuse pulmonary microthrombi on autopsy, all consistent with a vascular occlusive etiology of respiratory failure rather than the more classic findings of low-compliance in ARDS. The COVID-19 pandemic is overwhelming the world's medical care capacity with unprecedented needs for mechanical ventilators and high rates of mortality once patients progress to needing mechanical ventilation, and in many environments including in parts of the United States the medical capacity is being exhausted. Fibrinolytic therapy has previously been used in a Phase 1 clinical trial that led to reduced mortality and marked improvements in oxygenation. Here we report a series of three patients with severe COVID-19 respiratory failure who were treated with tissue plasminogen activator. All three patients had a temporally related improvement in their respiratory status, with one of them being a durable response.

In-Hospital Management and Outcomes of Acute Myocardial Infarction Before and During the Coronavirus Disease 2019 Pandemic.

The outbreak of coronavirus disease 2019 (COVID-19) has rapidly spread worldwide. This study sought to share our experiences with in-hospital management and outcomes of acute myocardial infarction (AMI) during the COVID-19 pandemic. We retrospectively analyzed consecutive AMI patients, including those with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI), from February 1, 2020, to April 15, 2020 (during the COVID-19 pandemic), and from January 1, 2019, to December 31, 2019 (before the COVID-19 pandemic), respectively. Fifty-three AMI patients (31 STEMI, 22 NSTEMI) during the COVID-19 pandemic were matched to 53 AMI patients before the pandemic. Baseline characteristics were comparable between the matched patients. STEMI patients during the COVID-19 pandemic had a longer delay time, less primary or remedial PCI and more emergency thrombolysis than those before the pandemic. Less coronary angiography and stenting were performed in AMI patients during the COVID-19 pandemic than before the pandemic. There were no statistically significant differences in the clinical outcomes between the matched patients. However, STEMI patients during the COVID-19 pandemic had a 4-fold (12.9% vs. 3.2%) increase in all-cause mortality rate compared with those before the pandemic. AMI combined with COVID-19 infection was associated with higher rates of mortality than AMI alone. This study demonstrates that the COVID-19 pandemic results in significant reperfusion delays in STEMI patients and has a marked impact on the treatment options selection in AMI patients. The mortality rate of STEMI patients exhibits an increasing trend during the pandemic of COVID-19.

Concerns for management of STEMI patients in the COVID-19 era: a paradox phenomenon.

The pandemic of coronavirus disease 2019 (COVID-19) has become a public health emergency of international concern. During this time, the management of people with acute coronary syndromes (ACS) and COVID-19 has become a global issue, especially since preexisting cardiovascular disease is a risk factor for the presence and the severity of COVID-19. The number of people with ST- elevation myocardial infarction (STEMI) has decreased during the pandemic and delays in the time looking for medical care have been reported. In addition, the diagnosis of ACS may have been difficult due to possible underlying myocarditis or other clinical entities. Regarding management of people with STEMI, although the superiority of primary percutaneous coronary intervention (PCI) over thrombolysis is well established, the notable exposure risks due to absence of negative pressure in catheterization rooms and the increased difficulty in fine manipulation on guidewires under proper protection equipment may contribute to the relatively secondary role of PCI during the COVID-19 pandemic; thus, fibrinolytic therapy or robotic-assisted PCI in early presenting STEMI patients may have an alternative role during this period if prevention measures cannot be taken. Healthcare stuff should take the proper measures to avoid the spread of and their exposure to the virus.

Optimization of resources and modifications in acute ischemic stroke care in response to the global COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has presented unprecedented challenges to healthcare organizations worldwide. A steadily rising number of patients requiring intensive care, a large proportion from racial and ethnic minorities, demands creative solutions to provide high-quality care while ensuring healthcare worker safety in the face of limited resources. Boston Medical Center has been particularly affected due to the underserved patient population we care for and the increased risk of ischemic stroke in patients with COVID-19 infection. METHODS: We present protocol modifications developed to manage patients with acute ischemic stroke in a safe and effective manner while prioritizing judicious use of personal protective equipment and intensive care unit resources. CONCLUSION: We feel this information will benefit other organizations facing similar obstacles in caring for the most vulnerable patient populations during this ongoing public health crisis.

Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19.

The global pandemic of coronavirus disease 2019 (COVID-19) is associated with the development of acute respiratory distress syndrome (ARDS), which requires ventilation in critically ill patients. The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response. A consistent finding in ARDS is the deposition of fibrin in the air spaces and lung parenchyma. COVID-19 patients show elevated D-dimers and fibrinogen. Fibrin deposits are found in the lungs of patients due to the dysregulation of the coagulation and fibrinolytic systems. Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI-1) from lung epithelium and endothelial cells create a hypofibrinolytic state. Prophylaxis treatment of COVID-19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre-existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue-type plasminogen activator (tPA), to treat COVID-19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID-19 patients to degrade fibrin and improving oxygenation in critically ill patients.