Thrombus Resolution Research Articles

Monocyte/macrophage-mediated venous thrombus resolution.

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.

Anticoagulantes Orais Diretos versus Antagonistas da Vitamina K para Trombo Ventricular Esquerdo: Uma Metanálise com Análise Sequencial de Ensaios

Abstract Background Vitamin K antagonists (VKAs) are the recommended first-line treatment for left ventricular thrombus (LVT); however, direct oral anticoagulants (DOACs) have been considered an alternative therapy. Objectives To evaluate the efficacy and safety of DOACs compared with VKAs therapy in patients with LVT. Methods PubMed, Embase, and Cochrane were systematically searched for randomized clinical trials or cohort studies that compared DOACs versus VKAs for LVT. Risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (95% CIs). Statistical significance was defined as p value < 0.05. Results A total of 4 randomized clinical trials and 29 cohort studies were included, with 4,450 patients assigned to either DOACs or VKAs. There was no significant difference between groups for stroke or systemic embolic (SSE) events (RR 0.84; 95% CI 0.65 to 1.07; p = 0.157), stroke (RR 0.73; 95% CI 0.48 to 1.11; p = 0.140), systemic embolic (SE) events (RR 0.69; 95% CI 0.40 to 1.17; p = 0.166), thrombus resolution (RR 1.05; 95% CI 0.99 to 1.11; p = 0.077), any bleeding (RR 0.78; 95% CI 0.60 to 1.00; p = 0.054), clinically relevant bleeding (RR 0.69; 95% CI 0.46 to 1.03; p = 0.066), minor bleeding (RR 0.73; 95% CI 0.43 to 1.23; p = 0.234), major bleeding (RR 0.87; 95% CI 0.42 to 1.80; p = 0.705), and all-cause mortality (RR 1.05; 95% CI 0.79 to 1.39; p = 0.752). Compared with VKAs, rivaroxaban significantly reduced SSE events (RR 0.35; 95% CI 0.16 to 0.91; p = 0.029) and SE events (RR 0.39; 95% CI 0.16 to 0.95; p = 0.037). Conclusions DOACs had a similar rate of thromboembolic and hemorrhagic events, as well as thrombus resolution, compared to VKAs in the treatment of LVTs. Rivaroxaban therapy had a significant reduction in thromboembolic events, compared to VKAs.

Intraluminal Thrombus of the Extracranial Cerebral Arteries in Acute Ischemic Stroke: Manifestations, Treatment Strategies, and Outcome.

Intraluminal thrombus (ILT) of the cervical arteries is an uncommon finding that can lead to acute or recurrent ischemic stroke. Currently, antithrombotic therapy in the form of antiplatelet and/or anticoagulation is considered the mainstay of treatment, but evidence of which one has a better outcome is lacking. A retrospective cohort study included 28 patients diagnosed with acute stroke or transient ischemic attack with ILT of the extracranial arteries from 2013 to 2022. The primary efficacy outcome was assessed as recurrent stroke, and the primary safety outcome was assessed as hemorrhagic complications. Secondary outcomes were assessed as the resolution of thrombi by CT angiography (CTA) and clinical improvement by the Modified Rankin Scale (mRS) and NIH Stroke Scale (NIHSS). Out of 28 patients, more than half (57.1%; n = 16) were males with a mean age of 57.8 ± 9.5 years and an average BMI of 26.9 ± 4.5 kg/m2. As initial treatment, twenty-four patients received anticoagulation and four received antiplatelet agents. Recurrent strokes were found in four patients (14.29%), and all were initially treated with anticoagulation. One patient in the anticoagulation group had a significant retroperitoneal hemorrhage. None of the patients in the antiplatelets group had a recurrent stroke or bleeding event. Initial treatment with antiplatelet agents significantly improved the NIHSS on day 7 (P = 0.017). A significant improvement in NIHSS on day 90 was observed in the anticoagulant group (P = 0.011). In the follow-up CTA performed on 24 patients, 18 (75%) showed complete resolution (3 out of 3 (100%) in the antiplatelet group and 15 out of 21 (71.43%) in the anticoagulant group). Initial treatment with anticoagulants improves neurologic outcomes in patients with ILT-induced acute ischemic stroke but carries the risk of recurrent stroke and bleeding. However, initial treatment with dual antiplatelet agents appears to have comparable efficacy without sequelae, particularly in atherosclerosis-induced ILT.

Outcomes of Portal Vein Tumour Thrombosis [PVTT] with Or Without Anticoagulation In 13 Patients Following in Vascular Department, Ttsh, Singapore

1.1. Aim: To look at the clinical outcomes in portal vein tumour thrombosis [PVTT] with or without anticoagulation. 1.2. Method: This study was approved by ethics committee. Patients following up in Vascular department were recruited with retrospective analysis from 2011 to 2016. Patients were classified into 3 groups: Portal vein thrombosis [PVT] with cirrhosis, malignancy, and infections. The biggest group was PVT with malignancy also known as portal vein tumour thrombosis [PVTT]. This group was analysed in this study. Statistical analysis was done with frequency, means, and percentages were calculated. Outcome measures were defined as clot resolution with or without anticoagulation, bleeding, recurrence, death. 1.3. Results: Out of 30 patients of PVT, 13 patients of PVTT were analysed in this study. They were primary hepatocellular carcinoma [HCC] in 4 and secondary HCC in 9 patients. Mean age was 66.8 years [range of 47-91 years]. There were 6 [46.2%] males and 7 [53.8%] females with ethnicity Chinese in 11 [84.6%], 2 [6.7%] Malay, other races 1 [7.7%]. Six patients received anticoagulation and 7 did not receive anticoagulation. 1.Of 6 patients who received anticoagulation, there was complete resolution of thrombus in 1 [16.7%], partial resolution in 0 [0.0%], no resolution in 5 [83.3%]. There was bleeding in 1 [16.7%], there was no recurrence and 4 [66.7%] died during the period of follow-up. 2.Of 7 patients who did not receive anticoagulation, there was complete resolution of thrombus in 0 [0.0%], partial resolution in 0 [0.0%], no resolution in 7 [100%]. There was bleeding in 0 [0.0%], there was recurrence in 0 [0.0%] and 4 [57.1%] died during the period of follow-up 1.4. Conclusion: Anticoagulation is of marginal benefit in terms of mortality in patient with PVTT. The rate of recurrence is similar in patients with or without anticoagulation, however, PVTT patients with anticoagulation is associated with increased risk of bleeding.

Two Cases of Thrombus Resolution Unrelated to Large Artery Atherosclerosis or Alteplase Use

Thrombus resolution is generally associated with a favorable prognosis. Patients with thrombus resolution often present with erythrocyte-rich thrombi, frequently associated with large artery atherosclerosis or alteplase use. This might explain the increased rate of cervical carotid artery occlusion and reduced incidence of atrial fibrillation in patients with thrombus resolution. However, recent reports have demonstrated that thrombus resolution can occur owing to several etiologies and various factors. We present two cases of thrombus resolution: one associated with internal carotid artery dissection and the other with a left atrial appendage thrombus. Notably, both were considered to be unrelated to large-artery atherosclerosis or alteplase use.

Chronic Thromboembolic Pulmonary Hypertension: A Review of the Multifaceted Pathobiology.

Chronic thromboembolic pulmonary disease results from the incomplete resolution of thrombi, leading to fibrotic obstructions. These vascular obstructions and additional microvasculopathy may lead to chronic thromboembolic pulmonary hypertension (CTEPH) with increased pulmonary arterial pressure and pulmonary vascular resistance, which, if left untreated, can lead to right heart failure and death. The pathobiology of CTEPH has been challenging to unravel due to its rarity, possible interference of results with anticoagulation, difficulty in selecting the most relevant study time point in relation to presentation with acute pulmonary embolism (PE), and lack of animal models. In this article, we review the most relevant multifaceted cross-talking pathogenic mechanisms and advances in understanding the pathobiology in CTEPH, as well as its challenges and future direction. There appears to be a genetic background affecting the relevant pathological pathways. This includes genetic associations with dysfibrinogenemia resulting in fibrinolysis resistance, defective angiogenesis affecting thrombus resolution, and inflammatory mediators driving chronic inflammation in CTEPH. However, these are not necessarily specific to CTEPH and some of the pathways are also described in acute PE or deep vein thrombosis. In addition, there is a complex interplay between angiogenic and inflammatory mediators driving thrombus non-resolution, endothelial dysfunction, and vascular remodeling. Furthermore, there are data to suggest that infection, the microbiome, circulating microparticles, and the plasma metabolome are contributing to the pathobiology of CTEPH.

Pulmonary Embolism Successfully Treated with Tenecteplase: A case report

Acute pulmonary embolism is a life-threatening situation when presenting with hypotension is called high-risk (massive) pulmonary embolism (PE) which is associated with mortality, especially if there is hemodynamic instability, right ventricular dysfunction with thrombus. Thrombolytic therapy can be lifesaving and leads faster improvement in hemodynamics in patients with acute pulmonary embolism and cardiogenic shock which accelerates the resolution of thrombus, reduction of RV dilatation, mortality and recurrent PE. Only three fibrinolytic agents namely Recombinant tissue-type plasminogen activator (rtPA), Streptokinase and Urokinase have been approved in the treatment of PE. We report the case of a 64 years old Bangladeshi female with a history of immobilization due to unilateral cut injury of foot, who presented with shortness of breath and intermittent chest pain for a duration of 7 days during OPD visit. ECG showed sinus tachycardia (HR-120bpm, regular) and poor progression of R wave. Echocardiography revealed dilated RV, PA with RV dysfunction, presence of McConnell’s sign, RV apical & PA thrombus, flattened IVS, PHT, and minimal pericardial effusion, normal LV systolic function which was reported as suspected pulmonary embolism. Urgent hospitalization and CT pulmonary angiogram (CTPA) was done for confirmatory diagnosis which revealed large pulmonary thrombus in both right and left pulmonary artery. Thrombolysis with Tenecteplase (100ml) over 2 hours was started immediately along with intravenous normal saline and norepinephrine for hypotension, although, it was not recommended by the European Society of Cardiology (ESC) guideline, resulting a successful resolution of the PA thrombus and clinical improvement. She was discharged with oral anticoagulant Rivaroxaban. Bangladesh Heart Journal 2023; 38(2): 148-154

Survival Advantage Associated with Heterozygous Factor V Leiden Mutation in Sars-Cov-2-Infected K18-hACE2 Mice

The pathogenesis of coronavirus disease 2019 (COVID-19) complications in critically ill patients involves virus-mediated cellular damage in infected tissue and secondary organ damage associated with a hyperinflammatory response. The proinflammatory milieu can result in endothelial dysfunction, predisposing patients to thrombosis leading to a life-threatening condition known as COVID-19-associated coagulopathy (CAC) which is driven by cellular and molecular mechanisms that are still unclear. We developed a mouse model based on the K18-hACE2 transgenic mouse recapitulating many of the CAC-associated pathological findings observed in human patients offering a reliable animal model for the study of SARS-CoV-2 pathogenesis. Plasma analysis revealed virus-induced upregulation of endothelial activation markers and alterations of all the measured coagulation factors' activities, resulting first in increased vascular leakage in the lung on day 5 post-infection, followed by the appearance of focal hemorrhagic lesions potentially associated with local thrombotic events on day 7. The infection-associated procoagulant phenotype appeared as early as day 3 post-infection (p.i.). Prothrombin time showed a 1/3 reduction in the normal clotting time in males. The overall procoagulant state was also reflected in the alteration of Factor(F) VIII and FX activity increasing to ~150% compared to uninfected controls. FIX showed the most significant alteration and was ~200% of the normal activity on day 3 p.i. and gradually increased over time, reaching ~350%. We also observed an increase in the activity of FV starting 3 days p.i. at ~210% of the normal level and persisting unchanged up to day 7 p.i. As reported during human infections, FV activity increased without significant changes in protein concentration or FVa levels. Natural anticoagulant and fibrinolytic mechanisms were dysregulated during virus infection resulting in a profound imbalance in thrombus formation and resolution. Infected K18-hACE2 mice showed downregulation of plasma protein C concentration which was not associated with any alteration of liver function, while plasma protein S concentration remained unaltered. Given the procoagulant environment generated after SARS-CoV-2 infection, reducing activated protein C (APC) anticoagulant and cytoprotective activities by blocking APC's active site with the SPC-54 monoclonal antibody worsened disease outcome and brought the mortality rate from 50% to 90%. In this observed procoagulant pathological context, where we observe increased activity of FV and where a deficiency of APC functions resulted in increased mortality, it wouldn't be surprising to observe an even more severe phenotype with the addition of APC resistance. To test this idea, we generated K18-hACE2 mice harboring the homologous human FV Leiden (FV L) mutation (R504Q). The Leiden mutation in FV eliminates one of several sites in FVa that are substrates for proteolysis by APC, resulting in diminished inactivation of FVa by APC and preventing the formation of the anticoagulant form of FV that serves as a cofactor for protein S-dependent inactivation of FVIIIa by APC. Upon SARS-CoV-2 infection, the presence of the homozygous FV L mutation in K18-hACE2 mice didn't affect the severity of the disease as measured by body weight loss during the course of the infection, and homozygous mutated mice had the same mortality rate as FV WT mice. Surprisingly, K18-hACE2 male mice carrying a heterozygous FV L mutation were extremely protected from SARS-CoV-2 infection, as their mortality dropped from 50% to only 15%. Histological analysis reveals how heterozygous FV L mice displayed a great reduction in immune infiltrate-associated fibrin deposition, suggesting an unexpected protective role of this prothrombotic mutation in the development of CAC. The protective effect of FV L heterozygosity may be attributable to enhanced thrombin formation which boosts inflammation and enhanced APC generation controlling proinflammatory and prothrombotic signaling, thus showing a delicate balance achieved by FV L heterozygosity that was lost for FV L homozygosity. As seen also in mouse models of bacterial sepsis, such favorable effects associated with FV L support the somewhat counterintuitive speculation that a partial increase in thrombin production in the early phase of the infection may support the resolution of COVID-19 complications.

High-Density Lipoprotein Inhibits Microvascular and Arterial Thrombosis in Mice By Attenuating VWF Self-Association

Background: Von Willebrand factor (VWF) mediates platelet adhesion and aggregation in primary hemostasis and thrombosis. The thrombogenicity of VWF depends on its self-association into fibers and its ability to efficiently capture platelets under high shear stress. We have shown that high shear promotes self-association of VWF into hyperadhesive strands and fibers, and that this process can be enhanced by low density lipoprotein (LDL) and attenuated by high density lipoprotein (HDL). In a model of thrombotic microangiopathy induced by VWF infusion into ADAMTS13-deficient mice, HDL attenuated the thrombocytopenia induced by the VWF challenge, suggesting that HDL may attenuate other types of thrombosis. Aims: To study the effect of HDL on microvascular and arterial thrombosis in mice by intravital microscopy. Methods: Microvascular thrombosis was induced in ADAMTS13-deficient mice by (1) local stimulation of mesenteric venules with calcium ionophore, and (2) infusion of high doses of recombinant human VWF (rVWF). The effect of HDL on VWF-platelet thrombus formation and deposition in the microvasculature was monitored microscopically. Arterial thrombosis was induced in wild-type (WT) mice by (1) laser-induced cremaster injury, and (2) FeCl 3-induced carotid artery injury. The effect of HDL on arterial thrombosis was also monitored microscopically. Results: When we induced microvascular thrombosis with ionophore, ADAMTS13-deficient mice evinced robust local platelet adhesion, platelet string formation, and thrombus embolization. Time to thrombus resolution was significantly prolonged (about 15 min) compared to that in WT mice (< 5 min). In mice pretreated with HDL (100 mg/kg), platelet deposition was largely prevented, with only occasional single platelets adhering. The differences in the extent of thrombi deposition and time to thrombus resolution between HDL-treated and untreated mice were both statistically significant. In the VWF challenge microvascular thrombosis model, rVWF infusion into ADAMTS13-deficient mice induced platelet adhesion to endothelium-associated VWF fibers in the cremaster microcirculation, forming long strings on the walls of arterioles and venules. Many microvessels became completely occluded. The prothrombotic effect persisted over 90 minutes. In contrast, pretreatment with HDL (100 mg/kg) led to significantly reduced platelet adhesion and string formation. Vessel occlusion was almost completely prevented. When thrombosis was induced in the cremaster arterioles of WT mice, HDL pretreatment resulted in notably decreased platelet accumulation and fibrin deposition in growing thrombi. HDL pretreatment also destabilized the thrombi and led to frequent embolization. In the FeCl 3-induced carotid artery injury model, HDL pretreatment slowed thrombus growth, enhanced thrombus embolization, and delayed vessel occlusion. Conclusion(s): The results demonstrate that VWF self-association is an important mechanism promoting thrombosis in large and small vessels. Our results show that HDL possesses a novel antithrombotic effect by inhibiting VWF self-association, preventing thrombosis in both small and large vessels. These results suggest that increasing the plasma HDL level can be exploited to prevent and treat thrombotic microangiopathies and arterial thrombosis.

Clinical characteristics and outcomes of left ventricular thrombus patients with mildly reduced and preserved left ventricular ejection fraction

Abstract Background Abnormal left ventricular ejection fraction (LVEF) is associated with the development of left ventricular thrombus (LVT) following acute myocardial infarction and also in non-ischaemic cardiomyopathies. LVT formation in normal LVEF is less common. Purpose We aimed to describe the clinical characteristics and outcomes of patients with LVT and LVEF>40%, and compare them against patients with LVT associated with LVEF≤40%. Methods We retrospectively studied 551 consecutive patients with LVT from our tertiary centre’s echocardiography database between March 2011 and January 2021. We compared baseline co-morbidities and echocardiographic parameters between patients with LVT and LVEF>40% versus LVEF≤40%. The Kaplan Meier method with log-rank test was used to compare rates of thrombus resolution, stroke and all-cause mortality between the 2 groups. Multivariable Cox regression models were constructed to correct for potential confounders. Results Mean age of the study population was 59.8 ± 12.9 years old and 86/551 (15.6%) were female. LVT in patients with LVEF>40% made up 100/551 cases (18.1%), of which 91.0% were associated with ischaemic heart disease. Patients with LVEF>40% were younger and had fewer cardiovascular co-morbidities than their counterparts with LVEF≤40%, including a lower prevalence of hypertension, hyperlipidaemia, diabetes mellitus, ischaemic heart disease and heart failure (Figure 1). Patients with LVEF>40% more often had a smaller thrombus (mean diameter 14.1 ± 5.9 mm) compared to those with LVEF≤40% (mean diameter 17.2 ± 8.2 mm). LVT with LVEF>40% was independently associated with thrombus resolution (HR 1.42, 95% CI 1.08–1.87, p=0.013) corrected for anticoagulant use, as well as lower mortality (HR 0.49, 95% CI 0.26–0.94, p=0.031) corrected for baseline co-morbidities (Figure 2). LVEF did not influence stroke rates. Conclusions In patients with LVEF>40%, LVT was less common. These patients had fewer cardiovascular co-morbidities, developed smaller thrombi, were more likely to have thrombus resolution and had a lower mortality rate. However, overall stroke risk was similar to patients with a reduced LVEF.Figure 1:Baseline characteristicsFigure 2:Outcomes

Short versus long-term anticoagulation for left ventricular thrombosis resolution during vitamin k antagonist therapy

Abstract Background The optimal duration of anticoagulant therapy to achieve thrombus resolution and prevent cardioembolic events in left ventricular thrombosis (LVT) has not yet been established. Purpose The purpose of our study is to evaluate the incidence of LVT resolution at 3 versus 12 months of vitamin K antagonists (VKAs) therapy. Methods Consecutive patients diagnosed with LVT and treated with VKAs for at least 12 months at 5 anticoagulant outpatient clinics in Italy were retrospectively included. The primary effectiveness outcome was on-treatment thrombus resolution while the secondary was objectively documented on-treatment acute ischemic stroke, peripheral embolism, and myocardial infarction at 12-months follow-up. Safety outcomes were on-treatment major and clinically relevant non-major bleedings at 12-months follow-up as defined by the ISTH criteria. Cumulative incidences of thrombus resolution with 95% confidence intervals (CIs) were calculated while other outcomes were descriptively reported. Multivariable Cox hazards models were calculated using age, sex, reduced left ventricular ejection fraction (EF < 35%), VKAs monotherapy, and time in therapeutic range (TTR) below 60% as covariates for thrombus persistence at 12-months of follow-up. Results Out of 95 patients, 87 were finally included (Table) and 8 excluded due to the lack of relevant data. Median age was 67 years and 75.9% were men. A total of 64.4% of patients had acute myocardial infarction as risk factor for LVT development while 21.8% and 5.7% of patients had dilated and primary hypertrophic cardiomyopathy, respectively. A reduced EF and atrial fibrillation were present in 77.0% and 19.5% of patients, respectively. All but one patient received warfarin with a median TTR of 54%, and 35.5% of patients did not receive concomitant antiplatelet therapy. All included patients received VKAs for at least 12-months. The 3 and 12 month cumulative incidences (Figure) of thrombus resolution were 34.5% (95% CI, 24.7%-44.5%) and 68.3% (95% CI, 57.2%-77.1%), respectively. At multivariable Cox regression analysis, the presence of a reduced EF appeared to be associated with a higher risk of thrombus persistence at 12-months follow-up (Hazard Ratio 3.09; 95% CI 1.27-7.55; p=0.013). During 12-months follow-up, two patients (2.3%) had acute ischemic stroke at 4 and 7 months from the start of VKAs therapy. Three patients (3.4%) had a major and 5 (5.7%) a clinically relevant non-major bleeding that occurred within the first three months of VKAs. Conclusions A 12-month course of anticoagulant therapy with VKA appeared to be effective and safe in patients with LVT and appeared to be associated with a higher cumulative incidence of LVT resolution than a 3-month course. A reduced left ventricular EF was associated with a higher risk of LVT persistence. Whether anticoagulant agents with improved ease-of-use and safety profile are effective in this setting remains undefined.Baseline patients' characteristicsCumulative incidences of LVT resolution

Left ventricular thrombus in patients with heart failure with improved ejection fraction

Abstract Background This study sought to: (1) determine the prevalence of LV thrombus at baseline and at the time of recovered ejection fraction (EF) in patients with heart failure with improved ejection fraction (HF-imp EF), (2) examine clinical and echocardiographic factors associated with the presence of LV thrombus, and (3) determine the prevalence of thromboembolic events when LVEF was improved and oral anticoagulant (OAC) was discontinued. Methods and results Patients with nonischemic HF-imp EF defined as a baseline LVEF of ≤ 40%, a ≥ 10% increase from baseline LVEF, and a second measurement (6 months apart) of LVEF of > 40% were consecutively enrolled in advanced HF clinic in a tertiary center. Patients with recent myocarditis, recent coronary revascularization, active chemotherapy, hypertrophic cardiomyopathy, cardiac amyloidosis, and tachycardia induced cardiomyopathy were excluded. A total of 104 consecutive patients (age 51 ± 15 years; 66% were male) with HF-imp EF were included. Of these, 14 patients (14%) had LV thrombus at baseline. Baseline LVEDD, LVEF, and LV global longitudinal strain (GLS) were 61 ± 10 mm, 23 ± 15%, and -5.9 ± 3.3%, respectively. Younger age, absence of atrial fibrillation, receiving oral diuretics, lower LVEF, reduced LV GLS, and reduced RV free wall (FW) GLS were significantly associated with LV thrombus at baseline (p < 0.05 for all) (Table 1). All patients (100%) with LV thrombus at baseline received oral anticoagulants (OAC). At the median follow-up of 27 months, 14 (100%) had complete resolution of LV thrombus when LVEF > 40%. Of 14 patients, 11 (79%) who were in sinus rhythm discontinued OAC. After a median further follow-up of 27.4 months following OAC discontinuation, there was no thromboembolic event or all-cause mortality in these patients. One of 11 patients developed worsening LVEF and recurrent LV thrombus at 25 months after LVEF improvement (> 40%). Conclusions Approximately 1 in 6 patients with HF-imp EF had LV thrombus at baseline. LV thrombus formation was associated with more impaired LV and RV systolic function and myocardial deformation implicating more thromboembolic milieu. Complete resolution of LV thrombus occurred in all patients who were on OAC therapy at the time of imp-EF. Discontinuation of OAC when LVEF > 40% was safe. However, recurrent thrombus formation can occur when LV systolic function was deteriorated. Annual or bi-annual echocardiographic follow-up may be essential in these patients.

Current concepts of treatment for left ventricular thrombus: A sys-tematic meta-analysis comparing direct oral anticoagulants versus vitamin K-antagonists

Abstract Background/Introduction Left ventricular thrombus (LVT) is a dreaded complication after myocardial infarction (MI) and is traditionally treated with Vitamin K antagonists (VKAs) for 3-6 months. Despite a gap of evidence, the broad use of direct oral anticoagulants (DOACs) for other thromboembolic disorders has triggered an increasing off-label use for DOACs in LVTs and has stimulated for expanding research focusing on DOAC´s utility for patients with LVT. Purpose To assess the safety and efficacy of DOACs versus VKAs for the treatment of LVT with a systematic meta-analysis. Methods We conducted a systematic search according to the PRISMA guidelines to identify all existing studies comparing DOACs and VKAs for the treatment of LVT. Forest plots and pooled odds ratios have been calculated for major bleeding events, strokes and systemic embolism, and for thrombus resolution. Results We have included a total of 13 studies with a pooled sample size of 2243 patients. 601 patients (26.8%) were treated with DOACs and 1642 patients (73.2%) with VKAs. The mean age was 55 and 59 years in the DOACs and VKAs group and sex was equally distributed with a male predominance of 81% in both groups. As underlying heart disease, most patients suffered from acute or chronic ischemic cardiomyopathy and presented with a mean left ventricular ejection fraction (LVEF) of 32% at admission. Baseline characteristics of patients included in each primary study are summarized in table 1. The pooled odds ratio of stroke or systemic embolism in patients treated with DOACs versus VKAs was 0.84 (95% CI 0.59-1.19) (p= 0.32). Compared to VKAs, we suggest that the use of DOACs may be associated with a reduced risk for major bleeding incidents without reaching statistical significance (OR 0.63 (95% CI 0.39-1.04) (p = 0.07). LVT resolution was similar and independent of the antithrombotic regimen (OR 0.91 (95% CI 0.7-1.19), p=0.50). Conclusions Based on our meta-analysis we conclude that DOACs seem to be non-inferior to VKAs for the treatment of LVT in terms of thrombus resolution, stroke and systemic embolism, and bleeding incidents. Despite these promising findings, several important aspects such as the duration of anticoagulation, and the type and dosing of the DOAC agent are still poorly understood. To close the lack of evidence for DOACs in LVTs, an adequately powered, randomized trial is needed.

Predicting thrombus outcome during anticoagulation for left ventricular thrombus

Abstract Background Up to 22% of embolizations have been linked to left ventricular (LV) thrombosis. Oral anticoagulation (OAC) for at least 3 months is recommended for patients with LV thrombus, according to guidelines. The purpose of this study was to predict the resolution of thrombus in patients with LV thrombus who were taking OAC for 3 months. Methods We enrolled patients prospectively from 2020 to 2022 and retrospectively from 2013 to 2019 at a national center of cardiovascular diseases in China. Patients with a history of LV thrombus < 3 months were included. Eligible patients were administered OAC and scheduled for 3 months of follow-up visits. The primary efficacy outcome was the rate of thrombus resolution at 3 months. Safety outcomes and major cardiovascular adverse events were collected. The hazard ratio (HR) and 95% confidence intervals (CIs) were estimated with adjustment for covariates using Cox regression models. Results We identified a total of 380 eligible patients. The median age was 53 (41, 63) years and 310 (81.6%) patients were male. The main underlying etiologies were dilated cardiomyopathy (51.6%). 204 (53.7%) patients received non-vitamin K antagonist oral anticoagulants (NOACs) while the rest were on warfarin within 3 months. In multivariable analysis, patients with NOACs had a higher likelihood of thrombus resolution than those taking warfarin (HR 1.39, 95% CI 1.08 – 1.79, P = 0.011). Lower LV ejection fraction levels and smaller diameter or thickness of thrombi were also the dominant predictors of thrombus resolution followed by a faster heart rate, a higher white blood cell count, therapy of diuretics, beta-blocker, and parental anticoagulation during hospitalization (eight variables, all P < 0.05). At 3 months, 29 patients (7.6%) suffered major cardiovascular adverse events, including 26 emboli and 3 deaths. One patient (0.3%) experienced an ISTH major bleeding. Conclusions Patients with systemic anticoagulation and positive treatment for heart failure achieved a greater rate of thrombus resolution at 3 months. The option of oral anticoagulation might be favorable NOACs, and further randomized controlled studies are warranted to explore.Forest plot of multivariable analysis.

Differences in clinical characteristics and outcomes between patients with left ventricular thrombus following non-anterior and anterior ST-elevation myocardial infarction

Abstract Background Left ventricular thrombus (LVT) is a serious complication following ST-elevation myocardial infarction (STEMI), and occurs more frequently in anterior compared to non-anterior myocardial infarction (MI).1 There is limited data on the clinical characteristics and outcomes in patients with LVT following non-anterior MI. Purpose We aimed to describe the clinical characteristics and outcomes of patients with LVT following non-anterior MI, and compare them against patients with LVT associated with anterior MI. Methods We retrospectively studied 217 consecutive patients with post-STEMI LVT from our tertiary centre’s echocardiography database between March 2011 and January 2021. Trans-thoracic echocardiography was performed at day 2 or 3 post-MI. We compared baseline co-morbidities and echocardiographic parameters between patients with LVT following non-anterior versus anterior MI. The Kaplan Meier method with log-rank test was used to compare rates of thrombus resolution, stroke and all-cause mortality between the 2 groups. Multivariable Cox regression models were constructed to correct for potential confounders. Results Mean age of the study population was 56.0 (IQR 48.0, 63.0) years old and 16/217 (7.4%) were female. LVT following non-anterior MI made up 24/217 patients (11.1%), and included lateral (n=3), inferior (n=15), inferoposterior (n=4) and inferolateral (n=2) MI. Patients with LVT associated with non-anterior MI were older and more frequently had a history of ischaemic heart disease (Figure 1). These patients also had a lower median left ventricular ejection fraction (LVEF) of 29% compared to their counterparts with anterior MI (mean LVEF 38%). Rate of anticoagulation was lower in patients with LVT associated with non-anterior MI (75.0% versus 92.2%). There were no differences in rates of thrombus resolution between the 2 groups (Figure 2). Patients with LVT following non-anterior MI had a higher incidence of stroke, however this observation was not present after correction for baseline embolic risk (CHA2DS2-VASc score) and rate of anticoagulation. Mortality rates were similar in patients with LVT following non-anterior MI versus anterior MI, after correction for baseline co-morbidities as well as in-hospital mortality – as this was more likely due to acute MI complications rather than longer term consequences of LVT. Conclusions Patients with LVT following non-anterior MI are older with a greater prevalence of prior ischaemic heart disease. These patients had a greater rate of stroke and mortality, although baseline co-morbidities and less frequent use of anticoagulation may have contributed to these findings. This needs to be clarified in future prospective studies.Figure 1:Baseline characteristicsFigure 2:Outcomes

Multimodality imaging in cardiac masses

Abstract Background Cardiac masses (CM) are an extremely heterogeneous clinical scenario, including benign and malignant neoformations. After a first echocardiographic assessment, Cardiac Computed Tomography (CCT) together with Cardiac Magnetic Resonance (CMR) and 18-Fluorodeoxyglucose Positron Emission Tomography (18- FDG-PET) represent second line and third-line imaging techniques to determine the nature of the mass. However, data regarding their diagnostic performance and a standardized imaging algorithm are lacking. Purpose To evaluate the different roles of CCT, CMR, and PET in defining the nature of CMs and to propose an evidence-based, stepwise, diagnostic approach. Materials and methods Out of 312 patients with suspected mass from January 2000 and August 2022, we enrolled 87 patients who underwent CCT, CMR and 18-FDG-PET within a month from the initial evaluation. A definitive diagnosis was achieved by histological examination or, in case of cardiac thrombi, with radiological evidence of thrombus resolution after an appropriate anticoagulant treatment. For each imaging technique, we identified a model with the strongest predictors of malignancy at multivariate analysis and evaluated their ability to discriminate between benign and malignant neoformations. A multiple model with forwarding selection was performed to identify the strongest predictors of malignancy at CCT, CMR and 18-FDG-PET. Results CCT model included 4 variables (irregular margins, mass dimension, invasiveness, and not-hypodense lesion) with an Area Under the Curve (AUC) of 0.972, 95% Confidence Interval (CI) 0.94-1.0; CMR model included 3 parameters (invasiveness, pericardial effusion and irregular margins, AUC 0.976 with 95% CI 0.95-1.0); PET model included only cardiac maximum Standardized Uptake Value (SUVmax), with an AUC 0.87 (95% CI 0.74-0.971). When implemented with SUVmax, CCT and CMR models showed only a slight improvement in their discrimination ability (AUC 0.975 and 0.986, respectively). No statistical difference was observed between CCT and CMR models regarding their discrimination ability (AUC 0.972 vs 0.976, p=0.26). However, on a multiple model with forwarding selection evaluating CCT, CMR and PET variables, only the 3 MR parameters remained significant predictors of malignancy. Conclusion After a first echocardiographic assessment, the application of the CMR model may be the most accurate second-level investigation to discriminate between benign and malignant lesions. When CMR is not available, or the patient has contraindications to CMR, the CCT model performs similarly, and 18-FDG-PET provides a negligible advantage.

Diagnostic agreement between echocardiography and second-level imaging techniques in patients with cardiac masses

Abstract Background Cardiac masses (CMs) are a diagnostic dilemma in clinical practice and require multimodality imaging to assess malignancy, which is essential to guide the proper treatment. Aim To define diagnostic accuracy and agreement between echocardiographic features and second-level imaging techniques (cardiac computed tomography – CCT or cardiac magnetic resonance – CMR) in patients with CMs. Methods All consecutive patients with histologically confirmed cardiac masses from January 2004 to December 2020, undergoing CCT and/or CMR after echocardiographic assessment were enrolled. Six echocardiographic variables, namely infiltration, polylobate mass, moderate-severe pericardial effusion, inhomogeneity, sessile and non-left localization, were used to predict malignancy. Patients with more than 3 of these features were considered at higher risk of malignancy. For the patients before 2017, the choice of which second-level imaging to perform was up to the clinical cardiologist. Since 2017, the has been the result of a multidisciplinary discussion by the Heart Team. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, with radiological evidence of thrombus resolution after an appropriate anticoagulant treatment. The echo-vs-CCT agreement and echo-vs-CMR agreement were evaluated. Accuracy indicators (sensitivity, specificity, PPV, NPV, Cohen’s Kappa coefficient) were calculated by standard formulas. Results Out of 249 patients with histologically confirmed CM, 138 underwent a CCT and 112 a CMR, after the standard echocardiographic assessment. A complete agreement between the echocardiographic assignment (using the cut-off of 3 parameters as a marker for malignancy) and CCT was reached in 104 out of 138 cases (75.4%), ranging from 85.1 to 70.3% for benign and malignant cardiac masses, respectively. On the other side, the agreement between the echocardiographic assignment and CMR report was in 93 out of 112 cases (83%), ranging from 88.7 to 82% for benign and malignant cardiac masses. The agreement between these imaging techniques expressed as Cohen’s κ was higher for echocardiography versus CMR (k=0.73), compared to echocardiography versus CCT (k=0.61). These results were also confirmed by the higher diagnostic accuracy of echocardiography versus CMR compared to echocardiography versus CCT (87% vs 80%), with best values of sensitivity, and specificity, denoting good reliability between the first 2 techniques. Conclusions A multimodal imaging approach is mandatory in the diagnostic work-up of CMs. The CMR, after a standard echocardiographic assessment, turned out to be the most accurate second-level investigation to discriminate between benign and malignant masses. However, when CMR is not available or the patient has a contraindication, the CCT could still be reliable.

Sex-related disparities in cardiac masses: clinical features and outcomes

Abstract Background Cardiac masses (CM) represent a heterogeneous clinical scenario. Sex-related differences of these patients remain to be established. Purpose: To evaluate sex-related disparities in CMs regarding clinical presentation and outcomes. Material and Methods Thestudy cohort included 321 consecutive patients with cardiac mass enrolled in our Centre between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in case of cardiac thrombi, with radiological evidence of thrombus resolution after anticoagulant treatment. All-cause death at follow-up was evaluated. Multivariable regression analysis was performed to assess potential prognostic disparities between men and women. Results Out of 321 patients with CM, 172 (54%) were female. Women were more frequently younger (p=0.02) than men. Regarding CM histotypes, females were more frequently affected by benign masses (with cardiac myxoma above all), while metastases were more common in men (p<0.001). At presentation, peripheral embolism occurred predominantly in women (p=0.03). Echocardiographic features such as greater dimension, irregular margin, infiltration, sessile mass and immobility were far more common in men. Despite a better overall survival in women, no sex-related differences were observed in the prognosis of benign or malignant masses. In fact, at multivariate analyses, sex was not independently associated with all-cause death. Conversely, age, smoking habit, malignancy and peripheral embolism resulted independent predictors of mortality. Conclusion In a large cohort of heart masses, a significant sex-related difference in histotype prevalence was found: benign CMs affected female patients more frequently, while malignant tumours affected predominantly men. Despite better overall survival in women, sex does not influence prognosis in benign and malignant masses.

Abstract 17888: Apixaban versus Vitamin K Antagonists for Left Ventricular Thrombus: A Systematic Review and Meta-Analysis

Introduction: Left ventricular thrombus (LVT), a major complication following acute myocardial infarction, significantly contributes to the increased risk of stroke and systemic embolism. Although vitamin K antagonists (VKAs) are the first-line treatment for LVT, direct oral anticoagulants (DOACs) have emerged as a potential alternative. However, the comparative effectiveness and safety of DOACs and VKAs for LVT treatment remain uncertain. Research question: Is apixaban therapy more effective and safer than VKA therapy for LVT? Aim: To assess the efficacy and safety of apixaban compared with VKAs therapy in patients with LVT. Methods: We systematically searched PubMed, Embase, and Cochrane databases for studies comparing the efficacy and safety of apixaban versus VKAs. We applied the random-effects model to calculate odds ratios (OR) and the corresponding 95% confidence interval. Heterogeneity was assessed using I 2 statistics. All calculations and graphics were performed using R (version 4.2.3). Results: Three randomized clinical trials (RCTs) were included, with 109 patients assigned to either apixaban (56 patients) or VKAs (53 patients). Compared to VKAs, apixaban showed no significant impact on thrombus resolution (OR 0.69; 95% CI 0.11-4.50; p=0.70; I 2 =0%), stroke reduction (OR 0.91; 95% CI 0.09-9.38; p=0.93; I 2 =1%), clinically relevant bleeding (OR 0.21; 95% CI 0.02-1.99; p=0.17; I 2 =0%), or all-cause mortality (OR 0.65; 95% CI 0.11-3.78; p=0.63; I 2 =8%). Conclusions: Apixaban therapy showed similar efficacy and safety to VKAs for LVT. These findings support the use of apixaban as an alternative to VKAs in LVT treatment.

Abstract 12644: FlowTriever Percutaneous Aspiration Thrombectomy: A Promising Approach to Catch a (Throm)Bus In-Transit

Introduction: Clot-in-transit (CIT) is a life-threatening emergency that occurs in about 25,000 patients annually and is associated with high mortality due to rapid cardiopulmonary collapse. This is a case of right atrial (RA) CIT extending from existing IVC filter in a patient with pulmonary embolism (PE) who underwent successful FlowTriever® catheter-based thrombectomy. Description of Case: A 60-year-old male presented with progressively worsening dyspnea on exertion, generalized weakness and fatigue, intermittent chest pain, and right leg pain with immobility for several weeks. He had a history of deep vein thrombosis (DVT), PE in 2008 treated with 18-month of warfarin. IVC filter was placed at that time for unclear indication. His initial labs showed elevated troponin-I of 34 ng/mL and NT pro-BNP of 3542 pg/mL, atrial flutter with 2:1 conduction, incomplete right bundle branch block, and old inferior infarct on ECG. Imaging revealed an extensive bilateral PE with right ventricle (RV) to left ventricle (LV) ratio of 2.3. Transthoracic echocardiogram (TTE) showed global LV dysfunction with ejection fraction of 44%, RV strain, dilated IVC, and an 8.7-cm mobile CIT in IVC extending into RA. Despite being treated with Heparin infusion, patient remained persistently tachycardic and dyspneic. Given his clinical stagnation due to CIT and submassive PE, he underwent an invasive TTE-guided percutaneous IVC and pulmonary arterial thrombectomy using Inari FlowTriever® catheter. Repeated TTE showed complete resolution of atrial thrombus. There was improvement in pulmonary arterial pressure and symptoms immediately post thrombectomy, but atrial flutter persisted. He was eventually discharged the following day with betablocker and life-long duration of anticoagulation. At follow up, he had complete resolution of symptoms and normal sinus rhythm on ECG. Discussion: Although surgical embolectomy is considered first-line therapy, percutaneous thrombectomy should be considered early for CIT to prevent of cardiopulmonary deterioration and shorter hospital course. FlowTriever® is the first device not requiring a cardiopulmonary bypass circuit to be FDA cleared for RA CIT, particularly benefiting patients who are poor surgical candidates.