Intracardiac Thrombus Formation Research Articles

A CASE SERIES OF INTRACARDIAC THROMBOSIS REVEALING BEHCETS DISEASE IN MOROCCAN PATIENTS

Aim of the work: The clinical presentation of Behcets disease (BD) is varied, While cardiovascular effects such as pericarditis, acute myocardial infarction, conduction disorders, and valvular disease have been reported, they are infrequent. The formation of intracardiac thrombus, as seen in our patients, is an exceptional occurrence. Patients and methods: We present a retrospective study of 4 cases of intracardiac thromboses in a series of 50 patients followed for BD in our department (over a period of four years), The diagnosis is made on the basis of the criteria proposed by the International Study Group (ISG). Results: All were male, the mean age at the time of the ICT diagnosis was 29.5 years. The main presenting symptoms were hemoptysis, chest pain, and dyspnea. It was associated with pulmonary artery aneurysm in two cases, and pulmonary embolism in all cases. In three cases, echocardiography was sufficient to reach the diagnosis but, in one, the difficulty of differential diagnosis with a cardiac tumor has been raised. The diagnosis has been confirmed by examining the operative specimen histologically in the case of this deceased patient, who experienced postoperative complications. Three patients were treated with immunosuppressant agents, corticosteroids, and anti-TNF alpha, one of whom showed a good response to treatment. Conclusion: A potential diagnosis of BD should be considered if a patient presents with an intracardiac mass, this is especially relevant in young male patients.

Left atrial appendage morphology and function predict thromboembolic risk in patients with embolic stroke of undetermined sources

Abstract Introduction Embolic stroke of undetermined sources (ESUS) is supposed to be associated with intracardiac thrombus formation, in particular in the left atrial appendage (LAA). We aimed to investigate the impact of LAA morphology and function on thromboembolic risk condition (TRC) and LAA thrombus in ESUS patients. Methods 185 ESUS patients (mean age 68 ±13 years, 33% female) without history of AF were included. All patients underwent clinical evaluation by CHA2DS2-VASc and complete transthoracic and transesophageal echocardiography shortly after index ESUS (4 days, IQR 3-6). LAA function and LAA morphology were evaluated by conventional 2D and 3D echocardiography and speckle tracking strain. TRC was defined as combination of thrombus, sludge and spontaneous echo contrast (SEC) in LAA. Results In 185 study patients, following LAA types were found: chicken wing (LAA CW) 79 (43%), windsock 64 (34%), cactus 35 (19%), cauliflower 7 (4%) and multilobate LAA, defined as LAA with ≥ 1 lobe, in 115 (62%) of patients. TRC was found in 123 (67%) and thrombus formation in 29 (16%). LAA CW and multilobate LAA were independent predictors of TRC (OR 2.3 (CI 1.2 - 4.5), p= 0. 01 and OR 2.2 (CI 1.2 - 4.2), p= 0.02, respectively) and furthermore, LAA CW and LAA-Sr were independent predictors of LAA thrombus (OR 2.5 (CI 1.1 - 5.8), p=0.04 and OR 0.9 (CI 0.8 – 1.0), p<0.01, respectively), all adjusted for CHA2DS2-VASc-score. Conclusion LAA type CW, multilobate LAA and novel LAA strain predicted independently TRC and LAA thrombus, respectively. These results indicate that LAA morphology and function are important in assessment of thromboembolic risk in ESUS patients.Table 1.

Mechanisms and Prediction of Ischemic Stroke in Atrial Fibrillation Patients.

Atrial fibrillation (AF) is the most common arrhythmia in adults worldwide and represents an important burden for patients, physicians, and healthcare systems. AF is associated with substantial mortality and morbidity, due to the disease itself and its specific complications, such as the increased risk of stroke and thromboembolic events associated with AF. The temporal relation between AF episodes and stroke is nonetheless incompletely understood. The factors associated with an increased thromboembolic risk remain unclear, as well as the stroke risk stratification. Therefore, in this review, we intend to expose the mechanisms and physiopathology leading to intracardiac thrombus formation and stroke in AF patients, together with the evidence supporting the causal hypothesis. We also expose the risk factors associated with increased risk of stroke, the current different risk stratification tools as well as future prospects for improving this risk stratification.

Predicting Intracardiac Thrombus Formation in the Left Atrial Appendage Using Machine Learning and CT Images.

This paper proposes a comprehensive method for estimating thrombus formation factors in the left atrial appendage (LAA). First, using 3D CT (Computer Tomography) image data as input, classification of thrombus presence/absence is learned using 3D ResNet. Besides, 3D Grad-CAM is applied to the prediction results to visualize regions of interest in thrombus formation. Second, features are extracted based on the visualization of regions of interest. Using the extracted features and numerical data obtained from the hospital as input, a regression analysis is performed to predict the presence/absence of thrombus using LightGBM. Visualization of regions of interest using 3D ResNet and 3D Grad-CAM shows that the right inferior pulmonary vein and the LAA were particularly correlated with thrombus formation. Estimation of important factors for thrombus formation using LightGBM shows that the LAA ostium area has the greatest influence on thrombus formation.Clinical Relevance-This paper shows the factors that contribute to thrombus formation in the LAA from the viewpoint of three-dimensional structure. In addition, the features considered important in thrombus formation were identified by comparing a variety of features.

The risk factors of thrombus formation and the effect of catheter ablation on repetitive thrombus formation in patients with atrial fibrillation: a single center retrospective study in China

BackgroundAtrial fibrillation (AF) predisposes patients to the formation of atrial thrombi. The CHA2DS2-VASc score does not include all risk factors for atrial thrombosis. The present study is designed to explore the influencing factors of thrombus formation in patients with AF and to investigate the effect of catheter ablation (CA) on recurrent thrombosis in patients with a history of intracardiac thrombus.Methods(1) This study consisted of 1726 patients that underwent CA, among which 58 patients had a history of intracardiac thrombus prior to CA. The risk factors for thrombus formation were explored by comparing the baseline clinical characteristics of patients with and without atrial thrombus. (2) The left atrial appendage flow velocity (LAAFV) in patients with a history of intracardiac thrombus who were willing to undergo transesophageal echocardiography (TEE) at the latest follow-up were examined, and comparisons of the LAAFV was made before and after CA.ResultsThe median follow-up period is 13 months. Persistent AF was found to be the only independent risk factor affecting the formation of atrial thrombus among the investigated factors (OR 3.152; 95%CI 1.806–5.500; p < 0.001). Twenty-seven patients agreed to undergo TEE during follow-up, no clinical ischemic stroke events were recorded, no recurrent intracardiac thrombus formation was detected in patients, 15 patients maintained sinus rhythm (55.6%) during follow-up; successful CA significantly increased LAAFV (difference between latest evaluation prior to CA 17.46 ± 14.81 cm/s, p < 0.001).ConclusionsPersistent AF is the only independent risk factor for thrombus formation. Successful CA may improve the LAAFV and thereby decrease the risk of intracardiac thrombus formation.

Percutaneous Left Atrial Appendage Occlusion Therapy: Past, Present, and Future

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is increasing in incidence and prevalence worldwide. AF significantly increases the risk of intracardiac thrombus formation and, if left untreated, ischemic stroke. In patients with nonvalvular AF (NVAF), the left atrial appendage (LAA) has been determined to be the source of thrombus development in 91% to 99% of cases. In this regard, oral anticoagulants (OACs) have become the standard treatment for stroke prevention in most patients with AF; however, OACs are associated with a risk of bleeding complications, and their efficacy depends on optimal patient compliance. Among alternative approaches to embolic stroke prevention, surgical LAA excision for stroke prevention for valvular AF was attempted as early as the late 1940s. LAA excision remains recommended in surgical guidelines for patients with NVAF requiring open-heart coronary bypass or valvular replacement/repair surgeries. However, owing to the traumatic/invasive nature and suboptimal outcomes of conventional surgical LAA intervention, clinical application of this approach is limited in current cardiology practice. Percutaneous LAA occlusion (LAAO) is increasingly being performed as an alternative to OAC for stroke prevention, particularly in patients with elevated bleeding risk. Substantial progress has been made in percutaneous LAAO therapy since its inception approximately 20 years ago. This article systematically reviews the literature leading to the development of LAAO and the evidence-based clinical experience supporting the application of this treatment strategy for NVAF, with a focus on recently published critical evaluations of US FDA and CE mark approved LAAO devices. Future perspectives regarding knowledge and technology gaps are also discussed, recognizing the many ongoing clinical trials that are likely to be transformative and the critical unanswered questions regarding LAAO therapy.

Risk factors for intracardiac thrombus in peripartum cardiomyopathy: a retrospective study in China.

Peripartum cardiomyopathy (PPCM) are more vulnerable to intracardiac thrombus than other types of cardiomyopathies, although explicit anticoagulant strategy is not sure. Too aggressive anticoagulation therapy can lead to severe bleeding events. Hence, we want to construct a risk stratification model for intracardiac thrombus in PPCM patients. A total of 159 suspected PPCM cases were initially screened, whereas 123 confirmed cases were enrolled in the final analysis. The study population was randomly assigned as derivation group (N=83) and validation group (N=40). The derivation cohort was utilized to develop the model, and the validation cohort was used to internal validate the discriminatory ability of the model. Formation of intracardiac thrombus was detected in 22 patients. After adjusted by multivariable logistic regression analysis, left ventricle ejection fraction (LVEF, OR 0.772, 95% CI 0.665-0.897, P=0.001), haemoglobin levels (OR 1.050, 95% CI 1.003-1.099, P=0.038), and thrombocyte counts (OR 1.018, 95% CI 1.006-1.029, P=0.003) were identified as risk factors independently associated with intracardiac thrombus and were finally included in the tentative risk stratification model with a C-indexes of 0.916 (95% CI: 0.850-0.982, P<0.001). A score of ≤7 was regarded as low risk, 8-10 defined intermediate risk, and ≥11 defined high risk in our model. Internal validation showed good discriminatory ability of the model with a C-indexes of 0.790 (95% CI: 0.644-0.936, P=0.017). In our retrospective study, impaired LVEF, elevated haemoglobin levels, and high thrombocyte counts were regarded as independent risk factors for intracardiac thrombus in PPCM. A risk stratification model derived from these risk factors, which was economic and easily applicable in clinical practice, could rapidly and accurately identify PPCM patients with higher-risk of intracardiac thrombus.

Neurological Manifestations of Myocarditis.

Purpose of Review The present review discusses the neurological complications associated with myocarditis of different etiologies.Recent FindingsMyocarditis can be idiopathic or caused by different conditions, including toxins, infections, or inflammatory diseases. Clinical findings are variable and range from mild self-limited shortness of breath or chest pain to hemodynamic instability which may result in cardiogenic shock and death. Several neurologic manifestations can be seen in association with myocarditis. Tissue remodeling, fibrosis, and myocyte dysfunction can result in heart failure and arrhythmias leading to intracardiac thrombus formation and cardioembolism. In addition, peripheral neuropathies, status epilepticus, or myasthenia gravis have been reported in association with specific types of myocarditis.SummaryMultiple studies suggest the increasing risk of neurologic complications in patients with myocarditis. Neurologists should maintain a high suspicion of myocarditis in cases presenting with both cardiovascular and neurological dysfunction without a clear etiology.

Newly developed spontaneous echocardiographic contrast as a potential marker of intracardiac thrombus formation after a transcatheter edge-to-edge mitral valve repair

Newly developed spontaneous echocardiographic contrast as a potential marker of intracardiac thrombus formation after a transcatheter edge-to-edge mitral valve repair

Left atrial appendage structure predicts thromboembolic risk in 185 patients with crytogenic stroke/TIA without history of AF

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Akerhus University Hospital Dept. of Cardiology Background Cryptogenic stroke/TIA (CS) is supposed to be associated with intracardiac thrombus formation and left atrial (LA) structure, in particular thrombus formation in left atrial appendage (LAA). However, there is little evidence if thromboembolic risk is associated with LAA morphology in patients with CS. Purpose We aimed to investigate, if different LAA morphology types may predict thromboembolic risk in patients with CS. Methods In this prospective study (mean follow-up 859 ± 226 days), 185 patients with CS (mean age 68 ±13 years, 33% female) without history of AF were included. All patients underwent complete transesophageal echocardiography in sinus rhythm after index CS (mean 5 ± 3days). Occurrence of LAA thrombus, sludge or spontaneous echo contrast (SEC) were defined as thromboembolic risk and LAA structure was evaluated by 2D and 3D transesophageal echocardiography. Multilobate LAA was defined as LAA with &amp;gt; 1 lobes. Results Of the 185 included patients, LAA type chicken wing was found in 79 (43%), type windsock in 64 (35%), type cactus in 35 (19%) and type cauliflower in 7 (4%). Thrombus formation occurred in 29/185 (16%), LAA sludge in 112/185 (61%), and LAA SEC in 74/185 (40%), which is increased compared to data in the general population. We found SEC in sludge in 65/112 (58%), SEC in thrombus in 18/29 (62%) and sludge in thrombus in 27/29 (93%). SEC and sludge were significantly associated with thrombus formation, (p &amp;lt; 0.001 and p &amp;lt; 0.01, respectively). Finally, thromboembolic risk occurred in 123 (67%) of all patients with CS. Moreover, LAA type chicken wing was significantly associated with thromboembolic risk (p &amp;lt; 0.01), while all other LAA types were not. Multilobate LAA occurred in 115 (62%) of all patients and predicted thromboembolic risk vs. non-lobated LAA (p= 0.04). In a multivariate analysis LAA type chicken wing and multilobate LAA were independently predictors of thromboembolic risk, figure 1. Conclusions Patients with cryptogenic stroke/TIA without history of AF showed increased thromboembolic risk, and SEC and sludge were significantly associated with LAA thrombus formation. Only LAA type chicken wing and multilobate LAA predicted independently thromboembolic risk in this study. Abstract Figure.

Thromboembolic characteristics and role of anticoagulation in long-standing Fontan circulation

IntroductionThe risk of thromboembolism increases with duration of Fontan circulation. Preventive drug strategies are still discussed controversially. We aimed to characterize clinical relevant thromboembolism in long-standing Fontan circulation and to analyse the protective effect of Acetylsalicylic acid (ASA) and Vitamin K Antagonists (VKA). Method78 patients (age ≥16 years) were included (mean age 20.7 ± 5.7 years; 51 male). Last medication and duration of therapy were documented. Perioperative events were excluded. Mean time of Fontan circulation was 21.1 ± 6.3 years, mean observation time 8.1 ± 5.6 years. Results44 patients were on VKA, 15 on ASA, 19 without treatment. Fifteen (19.2%) patients experienced thromboembolism. Nine patients had deep venous thromboses, among these five experienced pulmonary embolism. Four patients presented with supraventricular tachycardia (SVT), two with cerebral embolism and thrombus within the Fontan tunnel respectively. Two patients had an isolated thrombus in the Fontan tunnel. Time of Fontan circulation was significantly longer in thromboembolism (25.6 ± 8.3 years vs. 20.0 ± 5.2 years, p < 0.001). NYHA-class was worse (p = 0.03). Lacking treatment [OR 10.2 (95%CI 1.5–66.3)] and ASA [OR 1.25(95%CI)1.06–1.22] carried significantly higher risk of thromboembolism than VKA [OR 0.17 (95%CI 0.09–0.33)]. Kaplan-Meier analysis did n't differ in lacking treatment versus ASA (p = 0.2). VKA showed the best net-benefit regarding thromboembolism/bleeding complications (VKA: 11.4%, ASA 25%, VKA vs. lacking treatment 63.2%: p < 0.001). ConclusionIn long-standing Fontan circulation anticoagulation appears to be a safe treatment option to prevent late thromboembolism mainly caused by deep vein thrombosis and intracardiac thrombus formation associated with SVT.

Acute and chronic cardiac involvement in COVID-19

HintergrundNeben pulmonalen Manifestationen ist eine COVID-19-Infektion (Coronavirus-Krankheit 2019) häufig mit kardiovaskulären Komplikationen bzw. einer kardiovaskulären Beteiligung assoziiert. Das Herz kann im Rahmen einer Infektion sowohl direkt im Rahmen einer Myokarditis oder Perikarditis und auch im Rahmen von Hypoxie, Fieber, Volumenbelastungen oder thrombembolischer Komplikationen involviert werden. Bestehende kardiovaskuläre Grunderkrankungen haben zudem einen maßgeblichen Einfluss auf die Prognose von COVID-19-infizierten Patienten.MethodeDiese Übersichtsarbeit basiert auf einer umfassenden Literaturrecherche in der PubMed-Datenbank zu kardialen Beteiligungen und kardialen Komplikationen einer COVID-19-Infektion sowie deren Abgleich mit eigenen Erfahrungen.Ergebnisse und SchlussfolgerungJe nach Schweregrad der Infektion werden kardiale Beteiligungen im Rahmen einer COVID-19-Infektion mit bis zu 50 % durchaus häufig beobachtet. Neben der Echokardiographie als Untersuchungsmethode der ersten Wahl stellen die kardiale Magnetresonanztomographie (MRT) zur Beurteilung der myokardialen Struktur und die kardiale Computertomographie (CT) zur Beurteilung der Koronararterien bzw. zum Ausschluss eines intrakardialen Thrombus bedeutende Untersuchungsmodalitäten dar. Die wichtigsten kardialen Manifestationen einer COVID-19-Infektion sind entzündliche und ischämische Pathologien. Deren bildgebende Diagnostik spielt sowohl im akuten als auch im postinfektiösen Stadium eine bedeutende Rolle.

Presence of Intracardiac Thrombus at the Time of Left Ventricular Assist Device Implantation Is Associated With an Increased Risk of Stroke and Death

BackgroundHeart failure predisposes to intracardiac thrombus (ICT) formation. There are limited data on the prevalence and impact of preexisting ICT on postoperative outcomes in left ventricular assist device patients. We examined the risk for stroke and death in this patient population. Methods and ResultsWe retrospectively studied patients who were implanted with HeartMate (HM) II or HM3 between February 2009 and March 2019. Preoperative transthoracic echocardiograms, intraoperative transesophageal echocardiograms and operative reports were reviewed to identify ICT. There were 525 patients with a left ventricular assist device (median age 60.6 years, 81.8% male, 372 HMII and 151 HM3) included in this analysis. An ICT was identified in 44 patients (8.4%). During the follow-up, 43 patients experienced a stroke and 55 died. After multivariable adjustment, presence of ICT increased the risk for the composite of stroke or death at 6-month (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.00–3.33, P = .049). Patients with ICT were also at higher risk for stroke (HR 2.45, 95% CI 1.14–5.28, P = .021) and death (HR 2.36, 95% CI 1.17–4.79 P = .016) at 6 months of follow-up. ConclusionsThe presence of ICT is an independent predictor of stroke and death at 6 months after left ventricular assist device implantation. Additional studies are needed to help risk stratify and optimize the perioperative management of this patient population.

Left atrial 4D flow cardiovascular magnetic resonance: a reproducibility study in sinus rhythm and atrial fibrillation

BackgroundFour-dimensional (4D) flow cardiovascular magnetic resonance (CMR) allows sophisticated quantification of left atrial (LA) blood flow, and could yield novel biomarkers of propensity for intra-cardiac thrombus formation and embolic stroke. As reproducibility is critically important to diagnostic performance, we systematically investigated technical and temporal variation of LA 4D flow in atrial fibrillation (AF) and sinus rhythm (SR).Methods Eighty-six subjects (SR, n = 64; AF, n = 22) with wide-ranging stroke risk (CHA2DS2VASc 0–6) underwent LA 4D flow assessment of peak and mean velocity, vorticity, vortex volume, and stasis. Eighty-five (99%) underwent a second acquisition within the same session, and 74 (86%) also returned at 30 (27–35) days for an interval scan. We assessed variability attributable to manual contouring (intra- and inter-observer), and subject repositioning and reacquisition of data, both within the same session (same-day scan–rescan), and over time (interval scan). Within-subject coefficients of variation (CV) and bootstrapped 95% CIs were calculated and compared.ResultsSame-day scan–rescan CVs were 6% for peak velocity, 5% for mean velocity, 7% for vorticity, 9% for vortex volume, and 10% for stasis, and were similar between SR and AF subjects (all p > 0.05). Interval-scan variability was similar to same-day scan–rescan variability for peak velocity, vorticity, and vortex volume (all p > 0.05), and higher for stasis and mean velocity (interval scan CVs of 14% and 8%, respectively, both p < 0.05). Longitudinal changes in heart rate and blood pressure at the interval scan in the same subjects were associated with significantly higher variability for LA stasis (p = 0.024), but not for the remaining flow parameters (all p > 0.05). SR subjects showed significantly greater interval-scan variability than AF patients for mean velocity, vortex volume, and stasis (all p < 0.05), but not peak velocity or vorticity (both p > 0.05).ConclusionsLA peak velocity and vorticity are the most reproducible and temporally stable novel LA 4D flow biomarkers, and are robust to changes in heart rate, blood pressure, and differences in heart rhythm.

Myocardial infarction due to coronary embolism in a patient with dilated cardiomyopathy without atherosclerotic lesions on coronary angiography

Coronary embolism is a potential cause of reduced myocardial perfusion and ischaemia, which may clinically manifest as myocardial infarction. Data on the incidence of coronary embolism as a mechanism underlying acute coronary syndrome are limited. Coronary embolism should be suspected as a cause of acute coronary syndrome in patients without coronary angiographic evidence of atherosclerosis, but with risk factors for intracardiac thrombus formation. The most important of these are atrial fibrillation and dilated cardiomyopathy. We present a case of a patient in whom the diagnosis of myocardial infarction was justified by the coexisting dilated cardiomyopathy, and where coronary artery occlusion most likely occurred through the embolic mechanism. Differential diagnosis of the aetiology of acute coronary syndrome should be performed in patients with myocardial infarction without coronary atherosclerosis. This allows to implement individualised causative treatment, which may differ from standard management in myocardial infarction.

Postcardiotomy mechanical support in patients with mitral valve prostheses is associated with poor survival.

To elaborate on early survival in patients with mitral valve replacement requiring temporary extracorporeal life support system (ECLS). We analyzed survival, significant bleeding, wound infection, and ECLS duration in 421 from 14,400 patients with postoperative need for ECLS from January 2008 to December 2017 at our institution. Finally, patients were stratified according to the type of surgery performed: the mitral group (mitral valve replacement) n = 63 and the control group (any cardiac surgery excluding the mitral valve) n = 358. In order to adjust for preoperative patient characteristics, a propensity matching analysis was performed. Differences in in-hospital mortality were analyzed accordingly. In-hospital mortality was significantly higher in the mitral group as compared to the control group before and after adjustment (p < 0.001). Median duration of ECLS was 4 days in both groups. Perioperative bleeding (p < 0.001) and wound infection (p < 0.001) also showed significant worse outcome parameters in the mitral group. The main causes of death in the mitral group were multiorgan failure, n = 48 (76%), stroke, n = 7 (12%), and intracardiac thrombus formation, n = 5 (10%). ECLS is associated with a high in-hospital mortality rate in patients after mitral valve replacement.

Heparan sulfate consumption as a potential mechanism of intra-cardiac thrombosis in SARS-CoV-2 infection

Cardiac injury occurs in up to 36% of hospitalized patients with COVID-19.1.Lala A. Johnson K.W. Januzzi J.L. et al.Prevalence and impact of myocardial injury in patients hospitalized with COVID-19 infection.J Am Coll Cardiol. 2020; 76 (533 LP - 546)https://doi.org/10.1016/j.jacc.2020.06.007Crossref Scopus (384) Google Scholar Exact mechanism of cardiac injury in COVID-19 is not well understood, but may relate to direct cardiomyocyte damage, coronary plaque destabilization, cytokine inflammatory response, and intracoronary microthrombi formation. Lindner et al.2.Lindner D. Fitzek A. Bräuninger H. et al.Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases.JAMA Cardiol. 2020; (Published online July 27)https://doi.org/10.1001/jamacardio.2020.3551Crossref PubMed Scopus (423) Google Scholar in an autopsy study identified SARS-CoV-2 RNA in the myocardium in 24 of 39 autopsy cases. However, none of the 39 patients had myocarditis. Plasma pro-inflammatory cytokine levels were increased in 16 patients, suggesting cytokine response as a plausible cause of cardiac injury in COVID-19. Early reports identified ACE2 as a receptor for the SARS-CoV-2. Clausen et al.3.Clausen T.M. Sandoval D.R. Spliid C.B. et al.SARS-CoV-2 infection depends on cellular heparan sulfate and ACE2.Cell. 2020; (Published online September 142020.07.14.201616)https://doi.org/10.1016/j.cell.2020.09.033Abstract Full Text Full Text PDF PubMed Scopus (531) Google Scholar have recently identified heparan sulfate as a co-receptor for ACE2, whereby SARS-CoV-2 binds to heparan sulfate, a negatively charged polymer, through a positively charged site adjacent to the ACE2 binding domain. Heparan sulfate is ubiquitously expressed in mammalian tissues, and ACE2 is broadly expressed in the arterial, capillary, and venous endothelial cells. Heparan sulfate also interacts with antithrombin, which subsequently undergoes conformation change, resulting in the generation of the active form of antithrombin. The active form of antithrombin inhibits the procoagulant factors Xa and thrombin (IIa) (Fig. 1). Additionally, Gue et al.4.Gue Y.X. Gorog D.A. Reduction in ACE2 may mediate the prothrombotic phenotype in COVID-19.Eur Heart J. 2020; 41: 3198-3199https://doi.org/10.1093/eurheartj/ehaa534Crossref PubMed Scopus (14) Google Scholar suggested that reduction in ACE2 activity may increase vascular permeability resulting in increased expression of tissue factor in subendothelial cells, leucocytes, and platelets with subsequent activation of coagulation and thrombosis. As SARS-CoV-2 binds heparan sulfate and ACE2 for cellular entry, it is possible that the high expression of ACE2 in the heart would facilitate an interaction between SARS-CoV-2 and heparan sulfate, leading to heparan sulfate consumption. A lower level of heparan sulfate would lead to a reduction in antithrombin activation creating a hypercoagulable state. Heparan sulfate also mediates antithrombin's anti-inflammatory activity.5.Liu J. Pedersen L.C. Anticoagulant heparan sulfate: structural specificity and biosynthesis.Appl Microbiol Biotechnol. 2007; 74: 263-272https://doi.org/10.1007/s00253-006-0722-xCrossref PubMed Scopus (108) Google Scholar Loss of antithrombin's anti-inflammatory activity can potentially lead to endothelialitis and subsequent endothelial injury and intra-cardiac thrombus formation. We believe that heparan sulfate consumption during SARS-CoV-2 cellular entry might play a role in the thrombotic events associated with COVID-19 infection.

LEFT ATRIUM THROMBUS ASSOCIATED WITH VENO-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION (VA-ECMO)

Extra corporeal membrane oxygenation, specifically the veno-arterial type (VA-ECMO) is an effective cardiac support device but has potential negative effects, such as poor myocardial rest, increased after load with subsequent pulmonary edema or decreased flow to the left side of the heart resulting in intra-cardiac thrombus formation. Hence, adequate left ventricular drainage and adequate anticoagulation are essential. We are presenting a patient who required central VA-ECMO, but developed a left atrial (LA) thrombus, which adversely affected his outcome. In VA-ECMO, thrombus formation in the left side of the heart is a potential harmful complication. Early recognition is an important step to arrange appropriate interventions, either early anticoagulation or the potential need for a LV vent to prevent stasis.

Difference in the prevalence of intracardiac thrombus on the first presentation of atrial fibrillation versus flutter in the pediatric and congenital heart disease population.

Guidelines recommend trans-esophageal echocardiography (TEE) for patients with atrial fibrillation (AF) or atrial flutter (AFL) for >48 h, due to risk of intracardiac thrombus formation. With growing evidence that AFL in adults with structurally normal hearts has less thrombogenic potential compared to AF, and the need for TEE questioned, we compared prevalence of intracardiac thrombus detected by TEE in pediatric and congenital heart disease (CHD) patients presenting in AF and AFL. Single-center, cross-sectional analysis for unique first-time presentations of patients for either AF, AFL, or intra-atrial reentrant tachycardia (IART) between 2000 and 2019. Patients were categorized by presenting arrhythmia (AF vs. AFL/IART), with the exclusion of other forms of atrial tachycardia, hemodynamic instability, chronic anti-coagulation before TEE, and presentation for a reason other than TEE examination for thrombus. A total of 201 patients had TEE with co-diagnosis of AF or AFL. Of these, 105 patients (29 AF, 76 AFL) met inclusion criteria, with no difference in age between AF (median 24.9 years; IQR 18.6-38.3 years) and AFL/IART (23.3 years; 15.4-38.4 years). The prevalence of thrombus in the entire cohort was 9.5%, with no difference between AF (13.8%) and AFL groups (7.9%), p = .46. Patients with thrombus demonstrated no difference in age, systemic ventricular function, cardiac complexity, or CHADS2/CHA2DS2VASc score at presentation. The risk for intracardiac thrombus is high in the pediatric and CHD population, with no apparent distinguishing factors to warrant a change in the recommendations for TEE, with all levels of cardiac complexity being at risk for clot.

Levels of platelet derived extracellular vesicles in the left atrial appendage are higher in patients with permanent atrial fibrillation

Abstract Introduction Atrial fibrillation (AF) is a frequent arrhythmic disease and one of the most important causes of thrombembolic disease due to intracardiac thrombus formation. The left atrial appendage has been identified as the structure, where thrombus formation typically takes place in AF patients. Previous studies have shown thrombus formation is more frequent in permanent, than in paroxysmal or persistent AF. Underlying causes for this finding, however, remain unclear. Recently, it has been shown, that large extracellular vesicles (Microvesicles, MVs) are mediators of platelet activation. The aim of this study is therefore to investigate if the AF subtype correlates with the regional abundance of platelet derived MVs in the left atrial appendage. Methods and results In order to address this question blood samples from 59 consecutive patients undergoing left and right atrial catheterization were collected from the right atrium (RA), the left atrium (LA) and the left atrial appendage (LAA). 49% of the patients had permanent AF, 34% had non-permanent AF and 17% had no history of AF. MVs were isolated from 150 μL citrate plasma by a four-step differential centrifugation protocol (20000g x 40 min as main pelleting step). The MVs were characterized by immunoblotting and nanoparticle tracking analysis. The size of the MVs ranged between 50 and 600 nm and the MVs were shown to carry typical markers such as Annexin V. For flowcytometric analysis and quantification, Calcein AM was used to identify vesicles and CD31-PE, CD41-APC, CD235a-PE-Cy7 were applied to differentiate between platelet-derived MVs (PMVs, CD41+ CD31+), endothelial cell-derived MVs (EMVs, CD41- CD31+) and Red blood cell-derived MVs (RMVs, CD235a+). Fluorescence minus one controls, a concentration row and detergent mediated degradation were used to confirm specific staining of MVs. Total MV numbers (Calcein + events) did not differ significantly between the three cardiac localizations. In the left atrial appendage, the proportion of PMV was significantly higher in permanent AF patients compared to non-permanent AF. EMV numbers only differed in the right atrium, where permanent AF patients exhibited significantly lower numbers of EMVs compared to no AF controls. No differences between the groups were detected for RMV. Conclusion In the present study, we found that PMV levels in the left atrial appendage correlate with the type of atrial fibrillation (permanent vs non-permanent). PMVs have been connected to platelet activation and thrombus formation. These results may help to better understand how different types of atrial fibrillation cause different rates of thrombus formation in the LAA. PMV and EMV numbers by AF subtype Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical Faculty University Bonn