Resolution Of Thrombosis Research Articles

Resistance exercise promotes the resolution and recanalization of deep venous thrombosis in a mouse model via SIRT1 upregulation

BackgroundEarly exercise for acute deep venous thrombosis (DVT) improves the patient’s symptoms and does not increase the risk of pulmonary embolism. However, information about its effect on thrombus resolution is limited. The aim of this study was to investigate the role of resistance exercise (RE) in thrombus resolution and recanalization and determine its underlying mechanisms. MethodsNinety-six C57BL/6 J mice were randomly divided into four groups: Control group (C, n = 24); DVT group (D, n = 24); RE + DVT group (ED, n = 24); and inhibitor + RE + DVT group (IED, n = 24). A DVT model was induced by stenosis of the inferior vena cava (IVC). After undergoing IVC ultrasound within 24 h post-operation to confirm DVT formation, mice without thrombosis were excluded. Other mice were sacrificed and specimens were obtained 14 or 28 days after operation. Thrombus-containing IVC was weighed, and the thrombus area and recanalization rate were calculated using HE staining. Masson’s trichrome staining was used to analyze the collagen content. RT-PCR and ELISA were performed to examine IL-6, TNF-α, IL-10, and VEGF expression levels. SIRT1 expression was assessed using immunohistochemistry staining and RT-PCR. VEGF-A protein expression and CD-31-positive microvascular density (MVD) in the thrombus were observed using immunohistochemistry. ResultsRE did not increase the incidence of pulmonary embolism. It reduced the weight and size of the thrombus and the collagen content. Conversely, it increased the recanalization rate. It also decreased the levels of the pro-inflammatory factors IL-6 and TNF-α and increased the expression levels of the anti-inflammatory factor IL-10. RE enhanced VEGF and SIRT1 expression levels and increased the MVD in the thrombosis area. After EX527 (SIRT1 inhibitor) was applied, the positive effects of exercise were suppressed.ConclusionsRE can inhibit inflammatory responses, reduce collagen deposition, and increase angiogenesis in DVT mice, thereby promoting thrombus resolution and recanalization. Its underlying mechanism may be associated with the upregulation of SIRT1 expression.

661 TWO CARDIOMYOPATHIES IN ONE HEART: LESSONS FROM CLINICAL CASE

Abstract Case description In November 2020, a 55-years-old female with no significant past medical history, was admitted to our Emergency Department for chest pain after acute stressful event. She had a significant family history of ischemic heart disease, and unclear comatose status of her sister. At admission, she was asymptomatic, blood pressure was 115/80 mmHg, and oxygen saturation was 96%. An electrocardiogram (ECG) showed biphasic T wave in anterolateral leads. Elevated levels of troponin I (hs-TnI of 900 ng/L) and B-type natriuretic peptide (BNP) of 864 pg/mL were detected. Transthoracic echocardiogram (TTE) revealed an ejection fraction (EF) of 30% with apical ballooning of mid and apical segments of the left ventricle (LV) along with a sizable apical thrombus. Aspirin, iv diuretics, iv nitrates and unfractioned heparin were started. After 13 hours, she suffered a sudden transient neurological sign of decreased level of consciousness. Cranial MRI revealed an ischemic lesion in the territory of the apex of basilar artery (thalamic region). After 7 days from stroke, the patients underwent coronary angiography demonstrating unobstructed coronaries. Thus, the diagnosis of takotsubo syndrome was confirmed. During hospitalization, ECG evolution showed T wave inversion in precordial and lateral leads. Hs-TnI declining within normal values. Of note, ventricular arrhythmias burden with polymorphic ventricular contraction (PVC) emerged on continuous ECG-monitoring. Despite resolution of apical balloning and apical thrombosis, there were persistent wall-motion abnormalities in infero-lateral walls and mild LV dysfunction. This was also confirmed by cardiac magnetic resonance (CMR). Further, CMR also showed an intense myocardial edema with elevated LV mass. The patients was discharged on Warfarin, Bisoprolol 2.5 mg/die, Ramipril 5 mg/die, Eplerenone 25 mg/die. A clinical documentation was required to further investigate history of her sister, and neurological sequelae after cardiac arrest at 28s related to ventricular fibrillation emerged. However, no deeply evaluation of underlining heart disease was available. Despite an early favorable follow-up of patient, after six months, she suffered from palpitations and heart failure requiring diuretic therapy. Persistent repolarization abnormalities in infero-lateral leads, and low-voltage in precordial leads were noted. An extensive wall-motion abnormalities and moderate LV dysfunction were detected. Importantly, significant arrhythmic burden with PVC (13%) at 24-hr ECG monitoring was recorded. CMR was requested to further investigate the possibility of underlining coexisting cardiomyopathy. Mild LV dilation, moderate dysfunction (LVEF 39%), wall motion abnormalities and thinning of the inferior wall middle segments were reported. Surprisingly, fibro-fatty replacement in infero-lateral of LV wall was detected, and unexpectedly, right ventricular (RV) fibro-fatty replacement and mild RV dysfunction were also described. Hence, diagnosis of arrhythmogenic cardiomyopathy was made. Since persistent arrhythmic burden despite optimized medical treatment, biventricular involvement, family history of SCD, an implantable cardioverter defibrillator in primary prevention was placed. Furthermore, genetic testing was required and extensive clinical family screening was suggested. Conclusion According to the clinical data collected, takotsubo and arrhytmogenic cardiomyopathy can coexist. A potential link between two myocardial heart disease may be identified in the future, especially among patients presenting takotsubo and long-term unfavorable outcome.

484 PAPILLARY FIBROELASTOMA OF THE AORTIC VALVE ASSOCIATED WITH MYOCARDIAL INFARCTION, COMPLICATED BY ELECTRICAL STORM AND ENDOVENTRICULAR THROMBOSIS

Abstract Introduction Papillary fibroelastomas (PFE) are reported to be the most common tumors of the heart valves and are a possible source of systemic embolism, including myocardial infarction. Case Report We report the case of a 67-year-old female with no background of cardiovascular disease, admitted to our hospital with worsening dyspnea and chest tightness over the prior 10 days. The ECG showed a sustained hemodynamically tolerated monomorphic ventricular tachycardia, successfully treated with antiarrhythmic therapy, and ECG in sinus rhythm revealed signs of previous anterior myocardial infarction. Transthoracic echocardiogram showed a severely depressed systolic function (LVEF 19%), akinesia and thinning of the anterior wall and of all middle-apical segments, complicated by left ventricular aneurysm and endoventricular thrombosis. In the ventricular side of right aortic coronary cusp a mobile, pedunculated mass of 12×8 mm was visualized. A subsequent TEE corroborated the suspicion of PFE. She underwent cardiac MRI which showed areas of transmural late enhancement in all akinetic segments. A coronary angiography revealed sub-occlusion of the mid-anterior descending artery with no angiographic evidence of coronary atherosclerosis elsewhere. In view of her reduced LVEF and history of VT, an ICD was implanted. She started oral anticoagulant therapy and complete resolution of the endoventricular thrombosis was evidenced. After several days of electrical instability, characterized by multiple episodes of ventricular tachycardia, the clinical course was characterized by progressive clinical and electrical improvement and she was discharged in good clinical conditions after four weeks. Due to the severe impairment of the systolic function, not susceptible to surgical remodeling and the high operative risk, no indication for surgical removal of the mass was made. Conclusion Aortic PFE carry a not negligible risk of acute coronary syndrome, electrical storm and sudden death. It should be considered as the cause of myocardial infarction, and not an incidental finding, especially in patients with no angiographic evidence of coronary atherosclerosis.

79 PERCUTANEOUS TREATMENT OF HIGH-MODERATE RISK PULMONARY EMBOLISM SUCCESSFULLY TREATED WITH LOCAL ULTRASOUND-ASSISTED THROMBOLYSIS

Abstract Objective A 74 y/o female presented at our emergency department with syncope and head trauma. At the physical examination she was dispnoic and tachycardic. Laboratory analysis showed elevated troponin and NT-proBNP. The TTE showed a dilated and dysfunctional right ventricle, 60/60 sign, elevated PAPs with flattening of interventricular septum. CT angiography showed massive pulmonary embolism (PE) affecting both branches of the pulmonary artery. The lower extremity venous ultrasound showed a long thrombus in the left distal tract of the common femoral vein, superficial femoral vein and popliteal vein. Methods The patient was admitted to the cardiac intensive care unit. Due to her worsening respiratory condition and her moderate-high early mortality risk PE with high risk of bleeding due to recent trauma, we decided to treat her with local ultrasound-assisted thrombolysis (Ekos). This combines ultrasound fragmentation of the thrombus with in situ reduced-dose thrombolysis. Two catheters were placed in the two pulmonary arteries through two right femoral venous accesses. The Ekos catheters were left on site for 6 hours and then removed without complications. Results The treatment was immediately effective and the clinical conditions improved within 24-48 hours. The follow up TTE showed improved right ventricle function with attenuated signs of PE. CT angiography at one week showed resolution of the vascular thrombosis. Our patient was discharged in good clinical conditions and with prescription of a NOAC. The monthly follow up was normal and any complication was referred. Conclusions A local thrombolysis technique is useful in intermediate-high risk patients at elevated bleeding risk. Future studies will shed light on the comparison between these catheter directed treatments and standard of care.

945 TRANSIENT LEFT VENTRICULAR THROMBOSIS TAKOTSUBO-RELATED

Abstract Background Takotsubo syndrome (TTS) is an increasingly widespread syndrome characterized by an acute and usually transient left ventricular (LV) dysfunction. Despite its transient nature, the acute phase can be characterized by serious complications such as LV thrombosis, as occurred in this case. Case description A 93-year-old woman was admitted to our emergency department due to a recent and self-limiting episode of acute chest pain. The ECG showed ST-elevation in leads V2, V3 and V4 (Fig.1), with cardiac biomarkers elevation. Transthoracic echocardiography (TTE) revealed apical akinesia and hypokinesia of the other LV segments with a severely reduced ejection fraction (EF 35%). Emergency coronary angiography showed normal epicardial coronary vessels. So, Takotsubo cardiomyopathy was hypothesized as diagnosis. A mass suspect for a thrombus was detected into the apex on day 3, despite a mild improvement of the other segments contraction (EF 40%), and clearly confirmed with the contrast echocardiography on day 5 (Fig.2). Unexpectedly, any LV thrombus was identified with cardiac MRI study performed on day 7 (Fig.3). Meanwhile, the patient never showed neurological disorders or other signs of thromboembolic complications. Echocardiography performed on day 11, before discharge, showed a great improvement of regional wall motion with residual LV apical hypokinesia (EF 55%) and no apical masses. Discussion This case emphasizes the need of frequent echocardiographic follow up in stress-induced cardiomyopathy, not only during the akinetic phase but also during the period of wall motion recovery, in order to diagnose and treat as soon as possible a LV apical thrombosis avoiding thromboembolic complications. We hypothesized that the early anticoagulation therapy combined with the initial improvement in LV wall motion facilitated the process of thrombosis resolution. Cardiac MRI played a relevant role in the comprehensive assessment of the functional and structural LV changes; the absence of late gadolinium enhancement (LGE) can be considered as a positive prognostic factor, indicating a complete resolution without residual fibrosis. Conclusion A multimodality imaging approach, based on a frequent echocardiographic follow up combined with cardiac MRI, is fundamental for an early diagnosis and a rapid treatment of LV thrombosis Takotsubo-related.

Direct oral anticoagulants for the treatment of left ventricular thrombosis: an updated systematic review and meta-analysis.

This meta-analysis aims to compare direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in the setting of left ventricular thrombosis (LVT). We systematically searched MEDLINE, Cochrane Library, Biomed Central and Web of Science for trials comparing DOACs versus VKAs in the setting of LVT and reporting outcome data on thrombosis resolution, stroke and bleeding. Fourteen studies were finally selected. The Mantel-Haenszel method with a random effect model was used for the pooled analysis. The primary outcome was the occurrence of LVT resolution. The secondary outcomes were the occurrence of stroke or bleeding during treatment. One thousand three hundred and thirty-two patients were included in the analysis for the primary outcome. Of these, 424 were treated with DOACs and 908 with VKAs. The pooled odds ratio (OR) for the primary outcome was 1.00 [95% confidence interval (95% CI) 0.77-1.31, I2 0.0%], reflecting equal effect in terms of thrombus resolution. Overall, 2290 patients, 608 on DOACs and 1682 on VKAs were included in the analysis of stroke occurrence, showing reduced risk of events in patients treated with DOACs (pooled OR 0.58, 95% CI 0.36-0.93; I2 0.0%) as well as for bleeding occurrence (number of patients included 2139; pooled OR 0.64, 95% CI 0.44-0.94; I2 0.0%). Compared with VKAs, we found DOACs to have similar efficacy on thrombus resolution and favorable effects on stroke reduction and bleedings. DOACs should be considered as an alternative treatment for LVT. Large prospective randomized clinical trials are needed to confirm this exploratory finding.

Lupus anticoagulant in an elderly woman with dementia: a clinical case report with many questions and few answers

We describe the clinical case of an elderly woman with dementia, suffering from bilateral soleal venous thrombosis, despite antithrombotic prophylaxis, after orthopedic surgery. An isolated anti-cardiolipin antibodies positivity, however pre-existing for at least seven years, was found in a patient with previous cerebral ischemia and treated intermittently with aspirin. During the coronavirus disease 2019 (COVID-19) pandemic lockdown, to promote patient compliance, we practiced anticoagulant therapy with edoxaban: resolution of venous thrombosis was achieved. Longlasting medical treatment is discussed.

Pharmacological reduction of coagulation factor XI reduces macrophage accumulation and accelerates deep vein thrombosis resolution in a mouse model of venous thrombosis

BackgroundDeep vein thrombosis (DVT) and post‐thrombotic syndrome (PTS) remain highly prevalent despite modern medical therapy. Contact activation is a promising target for safe antithrombotic anticoagulation. The anti‐factor XI (FXI) monoclonal antibody 14E11 reduces circulating levels of FXI without compromising hemostasis. The human recombinant analog, AB023, is in clinical development. The role of FXI in mediation of inflammation during DVT resolution is unknown. ObjectivesInvestigate the effects of pharmacological targeting of FXI with 14E11 in an experimental model of venous thrombosis. MethodsAdult wild‐type CD1 mice were treated with subcutaneous anti‐FXI antibody (14E11, 5 mg/kg) versus saline prior to undergoing surgical constriction of the inferior vena cava (IVC). Mice were evaluated at various time points to assess thrombus weight and volume, as well as histology analysis, ferumoxytol enhanced magnetic resonance imaging (Fe‐MRI), and whole blood flow cytometry. Results14E11‐treated mice had reduced thrombus weights and volumes after IVC constriction on day 7 compared to saline‐treated mice. 14E11 treatment reduced circulating monocytes by flow cytometry and macrophage content within thrombi as evaluated by histologic staining and Fe‐MRI. Collagen deposition was increased at day 3 while CD31 and smooth muscle cell actin expression was increased at day 7 in the thrombi of 14E11‐treated mice compared to saline‐treated mice. ConclusionPharmacologic targeting of FXI enhances the early stages of experimental venous thrombus resolution in wild‐type CD1 mice, and may be of interest for future clinical evaluation of the antibody in DVT and PTS.

Extracellular traps and the role in thrombosis.

Thrombotic complications pose serious health risks worldwide. A significant change in our understanding of the pathophysiology of thrombosis has occurred since the discovery of extracellular traps (ETs) and their prothrombotic properties. As a result of immune cells decondensing chromatin into extracellular fibers, ETs promote thrombus formation by acting as a scaffold that activates platelets and coagulates them. The involvement of ETs in thrombosis has been reported in various thrombotic conditions including deep vein thrombosis (DVT), pulmonary emboli, acute myocardial infarction, aucte ischemic stroke, and abdominal aortic aneurysms. This review summarizes the existing evidence of ETs in human and animal model thrombi. The authors described studies showing the existence of ETs in venous or arterial thrombi. In addition, we studied potential novel therapeutic opportunities related to the resolution or prevention of thrombosis by targeting ETs.

Target therapy for venous thrombosis: experimental extravagance or tangible future?

Anticoagulant therapy is considered to be a treatment and prophylaxis standard for venous thrombosis (VT). Despite the high efficacy and safety of modern anticoagulants, bleeding as the side effect remains a prominent unresolved problem that can limit their use. As interrelation between immune system and coagulation is the basis of immunothrombosis, immunosuppression could be considered an alternative in the target therapy for venous thrombosis. Endothelial activation due to the blood stasis and vein wall hypoxia together with proinflammatory mediators promote essential conditions for venous thrombosis. The key points of this process are also the platelets and leukocytes activation and neutrophil extracellular traps secretion. Inhibition of intercellular interactions by the adhesion and signal molecules deletion (P-selectins, galectins, HMGB1) can fully prevent thrombosis or significantly reduce the thrombus. The same effect is observed when platelets function is suppressed by GPIbα transformation, CLEC-2 deletion or von Willebrand factor deficiency. Neutropenia contributes to a change in the thrombus structure and density, and less often prevents its formation. In addition, one of the options for the VT prevention in the experiment is the introduction of resorption mediators, which are secreted by effector cells in the process of thrombosis resolution. Target therapy appears to be a promising method based on key links in the VT pathogenesis, which may allow avoiding typical complications of anticoagulant therapy.

Bivalirudin or Unfractionated Heparin for Anticoagulation in Pediatric Patients on Continuous Flow Ventricular Assist Device Support: Single-Center Retrospective Cohort Study

Bivalirudin is a direct thrombin inhibitor that is being increasingly used for anticoagulation in children after ventricular assist device (VAD) implantation. While the data on bivalirudin use in pulsatile flow VADs are growing, reports on its use in patients on continuous flow (CF) VAD as well as comparisons of associated outcomes with unfractionated heparin (UFH) remain limited. Retrospective cohort study. Single tertiary-quaternary referral center. All patients less than 21 years old on CF-VAD support who received bivalirudin or UFH for anticoagulation between the years 2016 and 2020. Not applicable. Clinical characteristics compared between the cohorts included time to target range of anticoagulation, markers of hemolysis, and prevalence of hemocompatibility-related adverse events such as major hemorrhagic complications, ischemic stroke, and pump thrombosis. In 42 unique patients (41 HeartWare HVAD [Medtronic, Minneapolis, MN], one HeartMate 3 LVAD [Abbott Laboratories, Abbott Park, IL]) during the study period, a total of 67 encounters of IV anticoagulation infusions (29 UFH and 38 bivalirudin) were retrospectively reviewed. In comparison with use of UFH, bivalirudin was associated with lesser odds of major bleeding complications (odds ratio [OR], 0.29; 95% CI, 0.09-0.97; p = 0.038). We failed to identify any difference in odds of major thrombotic complications (OR, 2.53; 95% CI, 0.47-13.59; p = 0.450). Eight of the patients (28%) on UFH were switched to bivalirudin due to hemorrhagic or thrombotic complications or inability to achieve therapeutic anticoagulation, while two of the patients (5%) on bivalirudin were switched to UFH due to hemorrhagic complications. Bivalirudin was used for a "washout" in eight cases with concern for pump thrombosis-six had resolution of the pump thrombosis, while two needed pump exchange. Use of bivalirudin for anticoagulation in patients on CF-VAD support was associated with lesser odds of hemorrhagic complications compared with use of UFH. Bivalirudin "washout" was successful in medical management of six of eight cases of possible pump thrombosis.

A CASE OF PERSISTENT IN-SITU PULMONARY THROMBOSIS DESPITE LONG-TERM ANTICOAGULATION THERAPY

TYPE: Case Report TOPIC: Pulmonary Vascular Disease INTRODUCTION: In-situ pulmonary thrombosis refers to de novo thrombus formation in the pulmonary arteries without any distant source. In-situ thrombosis has been associated with radiation therapy and lung lobectomy. However, little is known about thrombosis resolution after anticoagulation therapy. We present a case of a patient with a persistent pulmonary thrombus despite adequate anticoagulation therapy. CASE PRESENTATION: A 70-year-old male with a past medical history of chronic obstructive lung disease, right-sided lobectomy secondary to non-small cell lung cancer, and subsequent restrictive lung disease due to lobectomy and radiation therapy presented to the pulmonary clinic with shortness of breath. Further evaluation that included a CT scan of the chest with contrast revealed an incidental in-situ thrombosis in the right main pulmonary artery extending into the right upper lobar branch. There was no evidence of cancer recurrence. Previous imaging did not reveal a similar thrombosis. Venous duplex and echocardiography were normal. The patient was anticoagulated with rivaroxaban for over nine months and remained on anticoagulation. Despite this, follow-up imaging has not demonstrated resolution, propagation, or improvement of the thrombus. After optimization of his comorbidities, the patient has remained symptom-free. DISCUSSION: In-situ pulmonary thrombosis may be associated with prior lung radiation therapy and lobectomy. While studies have shown that most pulmonary embolisms resolve over three months with anticoagulation, little is known about the resolution of in-situ thrombosis. CONCLUSIONS: Pulmonary thrombosis may become chronic despite anticoagulation. Therefore, it may be clinically relevant to identify the speed of clot resolution for evaluating patients with suspected recurrent thrombosis. DISCLOSURE: Nothing to declare. KEYWORD: IN-SITU PULMONARY THROMBOSIS, RADIATION THERAPY, LOBECTOMY, ANTICOAGULATION

P224 PRIMITIVE DILATED CARDIOMYOPATHY IN YOUNG MAN NOT ELIGIBLE FOR CARDIAC TRANSPLANTATION: COMBINED USE OF DEFIBRILLATOR, CARDIAC CONTRACTILITY MODULATION (CCM) AND CARILLON

Abstract Acute heart failure refers to rapid or gradual onset of symptoms and/or signs of chronic heart failure due to precipitating factors. Many patients with heart failure progress into a phase of advanced heart failure, characterized by persistent symptoms despite maximal therapy. Prognosis remains poor, with high 1–year mortality. Prognostic stratification is important to identify the ideal time for referral to an appropriate center capable of providing advanced therapies. We present the case of a 36–year–old black homeless man was admitted to Cardiological intensive care unit for acute heart failure complicated by intermediate–high risk bilateral subsegmentary pulmonary embolism, left endoventricular thrombosis, severe biventricular systolic dysfunction and secondary severe mitral insufficiency. After infusional diuretic and anticoagulant therapy, coronary angiography was performed documenting non–obstructive epicardial coronary arteries. Thereafter the therapy with sacubitril/Valsartan was falled, due to marked hypotension. Due to the high risk of sudden cardiac death, a single–chamber ICD was implanted in primary prevention. He was not eligible for long–term mechanical assistance (VAD) implantation and/or heart transplantation from referral centers, because of the patient‘s precarious psychosocial background. Furthermore, in the fullness of his faculties, the patient refused this possibility for religious reasons. Discharged in fair compensation, after resolution of pulmonary embolism and intracavitary thrombosis, he was again hospitalized for an exacerbation of chronic heart failure. Once labile hemodynamic compensation was reached, a cardiac contractility modulation device (CCM) was positioned, with the aim of improving symptoms. After optimization of therapy, with persistence of severe symptoms despite optimal medical and device therapy, options for intervention on the mitral valve were evaluated before further deterioration of the clinical conditions. Since this is a highly symptomatic patient at high risk for surgery, we opted for a coronary sinus mitral annuloplasty repair with Carillon, performed in the absence of complications. At the follow–up there was a mitral regurgitant volume reduction, improvement symptoms, in the absence of further hospitalizations.

Intracranial Injection of Fibrinolytic Agent in a Patient with Iatrogenic Artery Thrombosis following Clipping of the Middle Cerebral Artery Aneurysm

The presented clinical case demonstrates a successful early diagnosis of artery occlusion after aneurysm clipping and resolution of thrombosis during urgent reoperation by intracranial intra-arterial injection of a fibrinolytic agent.

Complete primary aortic ascending thrombosis resolution after dabigatran therapy.

A 36-year-old man visited hospital with chest pain and shortness of breath since a few days. There was no medical history. Due to troponin elevation 0.07 µg/L (normal <0.04 µg/L), a triple rule out computed tomography (CT) was performed and showed an extensive thrombosis starting from the aortic arch across to the brachiocephalic artery, measuring 25 × 35 mm, irregular, polylobular, in the ascending aortic lumen, 5 cm below the aortic arch, and bilateral pulmonary embolism (Panels A and B). No clue for dissection or other wall pathologies were found, normal size of the ascending aorta, no sign of intramural haematoma, no hypercoagulable disease in the medical history, or blood investigations. Aortic ascending thrombus in a non-aneurysmal aorta is an extremely rare event and has potentially very severe complications, with a life-threatening risk of myocardial infarction and cerebral embolization. After 2 weeks of intravenous heparin administration, the CT follow-up showed no change of the thrombus size and we decided to prescribe dabigatran 150 mg b.i.d. The patient felt very well and therefore he refused surgical resection, despite of heart team consensus. After 8 weeks, we find the thrombus getting smaller in the suprasternal echocardiographic view compared with the first imaging (Video still image E and see Supplementary material online, Video S1). After 3 months, there was a complete resolution in the suprasternal echocardiographic view (Video still image F and see Supplementary material online, Video S2). The use of dabigatran leads to complete resolution and prevented the recurrence of the disease during 2-year follow-up (Panels C and D).

A Prospective Study to Evaluate the Effectiveness of Edoxaban for the Resolution of Left Atrial Thrombosis in Patients with Atrial Fibrillation.

Available evidence on left atrial (LA) thrombus dissolution in patients with atrial fibrillation (AF) largely refers to the use of vitamin K antagonist oral anticoagulants (VKAs), showing >50% thrombus resolution over a 4-week to 12-month treatment period. Available data on non-vitamin K antagonist anticoagulants (NOACs) in this setting are limited and derive from isolated case reports or observational small-sized investigations with dabigatran, rivaroxaban or apixaban. The aim of this study was to investigate the extent of thrombus resolution with edoxaban therapy in patients with AF and LA thrombosis. We conducted a prospective, observational, open-label pilot study in seven Italian institutions. We included a total of 25 patients with non-valvular AF and LA (or left atrial appendage (LAA)) thrombosis, documented by transesophageal echocardiography (TEE). All patients received edoxaban OD treatment (n = 23 on 60 mg daily; n = 2 on 30 mg daily) and underwent TEE examination after 4 weeks. The primary endpoint was the percentage of patients with complete thrombus resolution by TEE imaging at 4 weeks. The mean age of the study population was 68.3 ± 10.8 years with a female population of 16%. AF was permanent in all cases, with a mean arrhythmia duration of 4.3 ± 1.7 years. CHA2DS2-VASc and HAS-BLED scores were 3.2 ± 1.5 and 1.9 ± 1.1, respectively. We were able to demonstrate a complete thrombus resolution in 14 patients (56%) at 4 weeks. In patients with residual atrial thrombosis (n = 11), we observed a 15.4 ± 14.9% reduction in the thrombus area from baseline. As compared with patients without thrombus dissolution, those with thrombus resolution had a numerically lower-indexed LA diameter (27.9 ± 9.3 vs 34.8 ± 16.1 mm/m2), a smaller maximum thrombus area at baseline (45.5 ± 44.6 vs 63.9 ± 43.5 mm2), a higher left ventricular ejection fraction (47.4 ± 21.0% vs 38.4 ± 20.6%) and higher maximum LAA flow velocities (26.3 ± 15.2 vs 19.3 ± 10.0 cm/s). Figures on the percentage of thrombus resolution in this study are comparable to those reported in the literature for the other OACs. We conclude that, in patients with AF, the use of edoxaban is associated with a >50% resolution of atrial thrombus at 4 weeks, similar to studies using VKAs and the other NOACs (ClinicalTrials.gov identifier number: NCT034899395).

Clinical Profile and Long-Term Outcomes in Pediatric Cavernous Sinus Thrombosis

BackgroundPediatric cavernous sinus thrombosis (CST) is a rare condition with limited data regarding its clinical characteristics and long-term outcomes. The objective of this study was to describe the clinical and radiologic features, diagnostic evaluation, management, and long-term prognosis and to identify clinical variables associated with long-term outcomes in pediatric CST. MethodsA retrospective chart review of patients younger than 18 years diagnosed with a CST between 2004 and 2018 at a single center was conducted. ResultsWe identified 16 (M:F = 10:6) children with CST with a mean age of 7.6 years (10 days to 15 years) and average follow-up duration of 29 months (3 weeks to 144 months). The most common symptom and examination finding at presentation was eyelid swelling (n = 8). Six patients had bilateral CST. The most common etiologies were sinusitis (n = 5) and orbital cellulitis (n = 5). Treatments included antibiotics (n = 14), anticoagulation (n = 11), and surgery (n = 5). Only one patient died due to intracranial complications. Twelve patients had a normal examination at follow-up. None of the clinical variables including age (P = 0.14), gender (P = 0.09), use of antibiotics (P = 1.00) or anticoagulation (P = 1.00), surgery (P = 0.28), parenchymal abnormalities (P = 0.30), additional cerebral venous thrombosis (P = 0.28), and early versus late commencing of anticoagulation (P = 1.00) were significant when comparing patients with full/partial resolution versus those with no resolution of thrombosis on follow-up neuroimaging. ConclusionsOur study is one of the largest cohorts with the longest follow-up data for the pediatric CST. Most of our patients had favorable outcomes at follow-up. We found no statistical difference between clinical variables when comparing patients with full/partial resolution versus those with no resolution of thrombosis on follow-up neuroimaging.

Guideline-driven Therapy and Resolution of Upper Extremity Vein Thrombosis in Hospitalized Pediatric Patients

Pediatric upper extremity venous thromboses (PUEVT) primarily affects hospitalized children with central venous access devices (CVAD). Current treatment guidelines for PUEVT include therapeutic anticoagulation followed by CVAD removal when possible, however data supporting these recommendations are sparse, largely anecdotal, and based on extrapolation from adult literature, with virtually no data regarding their effectiveness in promoting thrombus resolution. We sought to investigate the effectiveness of guideline-driven therapy to promote resolution of superficial (UESVT) and deep (UEDVT) upper extremity thromboses as well as demographic and management determinants of thrombus resolution.

Efficacy and Safety Profile of Novel Oral Anticoagulants in the Treatment of Left Atrial Thrombosis: A Systematic Review and Meta-Analysis

BackgroundThe presence of left atrial/left atrial appendage thrombosis is associated with a higher risk of thromboembolic events in patients with atrial fibrillation. The optimal antithrombotic strategy is not established to date.ObjectiveOur aim was to compare the efficacy and safety profile of novel oral anticoagulants with warfarin in the treatment of left atrial/left atrial appendage thrombosis.MethodsWe conducted a systematic search in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and 3 Chinese databases for all randomized controlled trials and cohort studies (PROSPERO, CRD42021238952) from inception to 7 May 2021. Two authors independently performed the articles selection, data extraction, and quality assessment. The efficacy outcome was the resolution of left atrial/left atrial appendage thrombosis, and the safety outcomes were bleeding and stroke/transient ischemic attack.ResultsOne randomized controlled trial and 5 cohort studies were included, with a total of 353 patients. Compared with warfarin, novel oral anticoagulants were associated with increased probability of left atrial/left atrial appendage thrombosis resolution (OR = 2.20; 95% CI, 1.35–3.60; I2 = 0%). Compared with warfarin, novel oral anticoagulants had a similar risk of bleeding (OR = 0.91; 95% CI, 0.39–2.13; I2 = 0%). There was no evidence of increased risk of stroke/transient ischemic attack (OR = 0.42; 95% CI, 0.12–1.45; I2 = 0%).ConclusionsNovel oral anticoagulants were more effective than warfarin in promoting the resolution of left atrial/left atrial appendage thrombosis, without increased risks of bleeding and stroke/transient ischemic attack. Our study provides valuable insight into clinical practice. Further well-designed randomized controlled trials are needed to fully evaluate the benefits and risks in these patients. PROSPERO Registration No.: CRD42021238952.

Refractory Ascites with Intrahepatic Portal Thrombosis after Living Donor Liver Transplantation Successfully Treated by Splenic Artery Embolization and Apixaban (Case Report)

&lt;p&gt;Refractory ascites is a rare complication after liver transplantation, and its incidence ranges from 5% to 7%. A 56-year-old man diagnosed with HBV-LC with massive ascites underwent living donor liver transplantation. After transplantation, more than 1000 ml/day of ascites was steadily drained until two weeks after LT. CT showed intrahepatic Rt. portal vein thrombosis and many remnant collaterals with splenomegaly. We decided to embolize the proximal splenic artery and use apixaban to reduce portal flow and resolve the intrahepatic portal thrombosis. One day after splenic artery embolization, the patient’s ascites dramatically decreased. Three days later, he was discharged from the hospital. Three months later, a follow-up liver CT showed resolution of thrombosis and no ascites. Splenic artery embolization was an effective and safe procedure for portal flow modulation in portal hyertension. Apixaban was effective for partial portal vein thrombosis in a liver transplant recipient.&lt;/p&gt;