Patients with venous thromboembolism after spontaneous intracerebral hemorrhage: a review

Background Patients with spontaneous intracerebral hemorrhage (ICH) have a higher risk of venous thromboembolism (VTE) and in-hospital VTE is independently associated with poor outcomes for this patient population. Methods A comprehensive literature search about patients with VTE after spontaneous ICH was conducted using databases MEDLINE and PubMed. We searched for the following terms and other related terms (in US and UK spelling) to identify relevant studies: intracerebral hemorrhage, ICH, intraparenchymal hemorrhage, IPH, venous thromboembolism, VTE, deep vein thrombosis, DVT, pulmonary embolism, and PE. The search was restricted to human subjects and limited to articles published in English. Abstracts were screened and data from potentially relevant articles was analyzed. Results The prophylaxis and treatment of VTE are of vital importance for patients with spontaneous ICH. Prophylaxis measures can be mainly categorized into mechanical prophylaxis and chemoprophylaxis. Treatment strategies include anticoagulation, vena cava filter, systemic thrombolytic therapy, catheter-based thrombus removal, and surgical embolectomy. We briefly summarized the state of knowledge regarding the prophylaxis measures and treatment strategies of VTE after spontaneous ICH in this review, especially on chemoprophylaxis and anticoagulation therapy. Early mechanical prophylaxis, especially with intermittent pneumatic compression, is recommended by recent guidelines for patients with spontaneous ICH. While decision-making on chemoprophylaxis and anticoagulation therapy evokes debate among clinicians, because of the concern that anticoagulants may increase the risk of recurrent ICH and hematoma expansion. Uncertainty still exists regarding optimal anticoagulants, the timing of initiation, and dosage. Conclusion Based on current evidence, we deem that initiating chemoprophylaxis with UFH/LMWH within 24–48 h of ICH onset could be safe; anticoagulation therapy should depend on individual clinical condition; the role of NOACs in this patient population could be promising.

Safety and efficacy of percutaneous catheter-directed treatment for intermediate-high risk pulmonary embolism

Background Pulmonary embolism (PE) is globally the third most frequent acute cardiovascular syndrome, ranking high among the causes of cardiovascular mortality. Systemic thrombolytic therapy (STT) permits prompt reperfusion after pulmonary obstruction, nevertheless this treatment carries by itself an inherent risk of major bleeding events. Development of new therapies and interventions that allow us to achieve early lung reperfusion along with a reduced risk of bleeding are necessary. Purpose The aim of this study was to evaluate the safety and efficacy of percutaneous catheter-directed treatment (PCDT) on intermediate-high risk PE patients with high bleeding risk or contraindication for STT. Methods We consecutively included all patients with intermediate-high risk PE undergoing PCDT in two university hospitals. Clinical, echocardiographic and hemodynamic variables (pre and post PCDT) were collected, as well as major adverse cardiac and bleeding events during follow-up. Results Between February 2018 and January 2021, we included 30 consecutive patients admitted with intermediate-high risk PE who underwent PCDT. Median age was 60 years, interquartile range (IQR) 51–72, and 41% were women. 14 patients (46.6%) presented an absolute contraindication for STT, which was the main reason for performing PCDT. Catheter-directed local thrombolysis (CDLT) was performed in 27 (90%) patients and mechanical fragmentation-aspiration was performed in 12 (40%) of them. We observed a significant reduction in mean pulmonary artery pressure (mPAP, mmHg) after PCDT: 40±13 vs. 25±12, p<0.001; as well as in NT-proBNP concentrations (pg/ml) 48 hours post-PCDT: 4791±1077 vs. 2311±680, p=0.002, (Figure 1). Echocardiographic parameters of right ventricular (RV) dysfunction also experienced a significant improvement 72 hours post-PCDT: TAPSE (mm) 15±2 vs. 22±3, p=0.001, (Figure 2); basal RV diameter (mm) 51±4 vs. 41±2, p=0.001. During a median follow-up of 13 months, IQR (8–22), 1 patient died from non-cardiac cause and no patient presented a bleeding event. Conclusions PCDT for intermediate-high risk PE is safe and effective, producing an early reduction in mPAP, in prognostic biomarkers such as NT-proBNP, as well as an early improvement of classic echocardiographic parameters of RV dysfunction. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Surgical Treatment of Pulmonary Embolism and Chronic Thromboembolic Pulmonary Hypertension

: Venous thromboembolism clinically presents as deep venous thrombosis or acute pulmonary embolism and is globally recognized as the third most frequent acute cardiovascular syndrome after myocardial infarction and stroke. Although pulmonary embolism does not typically cause severe pulmonary hypertension in the acute setting, thrombus organization and fibrosis can lead to stenosis or obliteration of pulmonary arteries in a minority of patients, which in turn result in severe pulmonary hypertension and right heart failure. This disease is labeled chronic thromboembolic pulmonary hypertension and can occur after a single episode or multiple ones of pulmonary embolism. The cornerstone of pulmonary embolism treatment is medical therapy, whereas systemic thrombolytic therapy has to be considered for patients with hemodynamic instability. Given the current acceptable short-term surgical mortality, the potential of first-line surgical embolectomy as an alternative to medical thrombolysis has gained momentum as far as pulmonary embolism treatment is concerned. In contrast to pulmonary embolism, bilateral complete pulmonary endarterectomy under short deep hypothermic circulatory arrest intervals is the treatment of choice against chronic thromboembolic pulmonary hypertension, given patients’ operability. Pulmonary endarterectomy is suggested in every operable patient when the operation is offered by an experienced multidisciplinary team, including at least one experienced surgeon. Surgical embolectomy should also be limited to large institutions since it also requires an experienced heart team. This review concerns a thorough discussion regarding surgical treatment of pulmonary embolism and chronic thromboembolic pulmonary hypertension. Eligibility criteria, operation-related complications and postoperative outcomes are discussed in detail.

Submassive Pulmonary Embolism: Current Perspectives and Future Directions

Submassive pulmonary embolism (PE) lies on a spectrum of disease severity between standard and high-risk disease. By definition, patients with submassive PE have a worse outcome than the majority of those with standard-risk PE, who are hemodynamically stable and lack imaging or laboratory features of cardiac dysfunction. Systemic thrombolytic therapy has been proven to reduce mortality in patients with high-risk disease; however, its use in submassive PE has not demonstrated a clear benefit, with haemodynamic improvements being offset by excess bleeding. Furthermore, meta-analyses have been confusing, with conflicting results on overall survival and net gain. As such, significant interest remains in optimising thrombolysis, with recent efforts in catheter-based delivery as well as upcoming studies on reduced systemic dosing. Recently, long-term cardiorespiratory limitations following submassive PE have been described, termed post-PE syndrome. Studies on the ability of thrombolytic therapy to prevent this condition also present conflicting evidence. In this review, we aim to clarify the current evidence with respect to submassive PE management, and also to highlight shortcomings in current definitions and prognostic factors. Additionally, we discuss novel therapies currently in preclinical and early clinical trials that may improve outcomes in patients with submassive PE.

Letter to the Editor

I read the recent article by Apsey et al with interest, which recommended "the potential benefits of thrombolytic therapy in massive and submassive pulmonary embolism". This would appear to go against current NICE guidance which states "Do not offer pharmacological systemic thrombolytic therapy to people with PE and haemodynamic stability with or without right ventricular dysfunction". Both recent NICE and European pulmonary embolism (PE) guidance are clear that only high-risk PE (previously called 'massive') should routinely be thrombolysed.

Efficacy of thrombolytics in patients with acute coronary syndrome

Funding Acknowledgements Type of funding sources: None. Background/Introduction: The optimal choice of the thrombolytic drug for emergency revascularization in patients with acute coronary syndrome (ACS) still remains to be defined. Percutaneous coronary intervention is a more safe and effective method of reperfusion compared with thrombolytic therapy, that’s why the last is relatively not common nowadays. But in the COVID-19 era in a number of cases some patients with ACS can’t be quickly hospitalized due to different reasons like the absence of the nearest available cardiovascular center, or lack of an ambulance. A long period of chest pain forces the doctors to use systemic thrombolytic therapy. Purpose This study investigates the efficacy and safety of Alteplase, Prourokinase, Tenecteplase, and Streptokinase in patients with acute coronary syndrome. Methods A retrospective, open, non-randomized cohort study was conducted. We have analysed 600 patients with ACS, who underwent systemic thrombolytic therapy at the prehospital and in-hospital stages from 2009 to 2011. Patients were divided into several groups according to the thrombolytic agent administered: Alteplase (254 patients), Prourokinase (309 patients), Tenecteplase (6 patients), Streptokinase (31 patients). Treatments were to be given as soon as possible. The ECG reperfusion criterion was a decrease in the ST segment by 50% or more from the initial elevation. Results Among 600 patients (mean age, 61 years (SD = 20); 119 women [19.7%]), 440 had successful reperfusion. The median time from chest pain onset to the start of treatment was 3 hours (P < 0.001). The percentages of successful thrombolysis for each agent were similar: Alteplase 74,4% Prourokinase 71,2%, Tenecteplase 83%, Streptokinase 74,2%. No statistical differences were observed in thrombolytic results among these groups (OR: 0.60, 95% CI: 0,2868 to 1,217; P = 0.17). At the same time, the hospital treatment with prourokinase was more effective than prehospital care with prourokinase: 110 successful reperfusions in 138 patients (79.7%) and 110 successful reperfusions in 171 patients (64.3%), respectively. Regardless of the onset of the attack (OR: 0.45, 95% CI: 0,2004 to 0,9913; P = 0.05). The effectiveness of the other thrombolytics cannot be compared between prehospital care and hospital treatment due to the rare use at the hospital stage in our cases. In the study, there was also no statistical difference in complication rates among the treatment groups. Among all patients, there were 9 fatal outcomes (1.5%): Alteplase 3,15% Prourokinase 1,9%, Streptokinase 3,22%. Conclusion(s): In patients with ACS, all thrombolytic drugs showed similar effectiveness. There is no difference in the safety and efficacy among the agents in our study, but there is a difference in cost and route of administration. However, upcoming prospective trials with long follow-up periods might be expected to determine the most appropriate systemic thrombolytic drug.

Percutaneous catheter-directed treatment in intermediate-high risk acute pulmonary embolism. Hemodynanical and right heart function-related parameters changes and short-term outcomes

Funding Acknowledgements Type of funding sources: None. Introduction Acute pulmonary embolism (PE) is the third cause of cardiovascular mortality, right after acute myocardial infarction and stroke. Systemic thrombolytic therapy (SLT) restores pulmonary perfusion earlier than low molecular-weight heparin, but with a significantly higher risk of major bleeding. Currently, in our area there is a lack of standardized protocols for the management of patients in which SLT is contraindicated. Objective The purpose of our study was to evaluate the safety and efficacy of percutaneous catheter-directed treatment (PCT) for high-intermediate risk PE (HIRPE) patients with hemodynamic deterioration on anticoagulation treatment. Methods We consecutively included all patients with HIRPE patients who underwent PCT in our center. Before and after PCT clinical, echocardiographic and hemodynamic variables were collected, as well as events (major or minor bleeding, death) during follow-up. Results From February 2018 to February 2020, 20 patients with HIRPE underwent PCT. The mean age of our cohort was 62 (52 - 73), and 46.6% were women. The indication for PCT was absolute contraindication for SLT (9 patients, 45%), followed by high bleeding risk (8 patients, 40%) and failure of SLT. Vascular access was mainly performed through femoral vein (12 patients, 60%) followed by a peripheral vein of the superior limb (8 patients, 40%). During pulmonary angiography, lobar arteries occlusion was observed in 60% of the cases, with involvement of main pulmonary arteries in 40% of the cases. Local thrombolysis with Alteplase was performed in 17 cases (85%), and in 8 cases it was decided to carry-out a thrombus fragmentation-aspiration strategy. We observed and early improvement of hemodynamic parameters after PCT, with a significant reduction of mean pulmonary artery pressure before and after PCT (40 +/- 13 mmHg vs. 25 +/- 12 mmHg, p < 0.001, figure 1), as well as an improvement in systolic blood pressure (102 +/- 13 mmHg vs. 129 +/- 14, p < 0.001) and the partial pressure of oxygen (51 +/- 3 vs. 67 +/- 2, p = 0.002). We also observed a significant decrease in NT-proBNP values at admission and 48 hours after PCT (4791 +/- 1077 pg/mL vs. 2311 +/- 680 pg/mL, p = 0.002, figure 2), as well as an improvement in echocardiographic right ventricular function parameters evaluated at admission and 72 hours after PCT, such as TAPSE (15 +/- 2 mm vs 22 +/- 3 mm, p = 0.001) or right ventricle basal diameter (51 +/- 4 mm vs. 41 +/- 2 mm, p = 0.001). During a median follow-up of 7 months (4 - 12 months) one patient died of non-cardiac cause and none of them had a major or minor bleeding event. Conclusion PCT in patients with HIRPE with hemodynamic deterioration on anticoagulation is a simple and effective procedure with an immediate reduction of mean pulmonary pressure and an early improvement of right ventricle-related biochemical, hemodynamic and echocardiographic parameters. Abstract Figure 1: mPAP after and before PCT.