Marker Of Thromboembolic Risk Research Articles

Dynamic recommendation for anticoagulant treatment in patients with atrial fibrillation using deep reinforcement learning method

Abstract Background Recent evidence suggests that the guideline-directed anticoagulant therapy for atrial fibrillation (AF) remains controversial. Widely-used CHA2DS2-VASc score is solely based on limited traditional cardiovascular risk factors, omitting AF characteristics and other markers of thromboembolic risk. A more efficient, safer and more personalized anticoagulant approach is warranted. Purpose To develop a data-driven deep reinforcement learning (DRL) model for guiding dynamic anticoagulant treatment in AF patients to improve cardiovascular outcomes. Methods Participants of this study were enrolled from the multicentred China Atrial Fibrillation (China-AF) Registry between August 2011 and December 2022, who were with regular follow-up every 6 months. We excluded patients on warfarin at baseline due to its declining usage trend in non-valvular AF patients in China. The DRL model was trained in 70% randomly selected patients for optimal dynamic decision-making, and then subsequently tested in the remaining 30%. Data of sociodemographic characteristics, AF characteristics, medical history, lifestyle factors, laboratory examination, and medications were input for model training. Concordance rate between DRL model’s recommendations and physicians’ actual decisions of non-vitamin-K-antagonist oral anticoagulant (NOAC) prescription among all visits before censoring was calculated for each patient. Primary outcome was the composite of cardiovascular death, ischemic stroke, transient ischemic attack or systemic embolism (SSE), and major bleeding. Shapley additive explanation analysis ranked the most important factors affecting decision-making of the DRL model. Results A total of 20068 patients (mean age: 63.0±12.0 years; 36.2% female) were randomly divided into a training cohort of 14050 patients and a testing cohort of 6018 patients. The model’s NOAC recommendations were mostly affected by age, prior NOAC prescription, body mass index, hypertension history and prior statin prescription (Figure 1). Patients with concordance rates of 50.1%-75% and 75.1%-100% had significant risk reductions for the primary outcome (adjusted HR =0.63; 95% CI, 0.46-0.85; P = 0.003 and adjusted HR =0.59; 95% CI, 0.46-0.75; P <0.001, respectively), compared to those with a concordance rate of 0-25%. Similar results were observed for all-cause death, cardiovascular death and SSE outcomes, that patients with the highest concordance rate had a significant lower risk, compared to those with the lowest concordance rate. There was a nonsignificant but similar trend with regard to major bleeding events (Figure 2). Conclusions This modelling study suggests that a data-driven DRL model might provide more efficient, safer and more personalized anticoagulant suggestions, potentially assisting physicians in clinical practice.

Platelet Function and Turnover in Essential Thrombocythemia: A Systematic Review.

Essential thrombocythemia (ET) is a myeloproliferative neoplasm characterized by increased platelet counts. ET has an incidence of 0.6 to 2.5 per 100,000 per year in Europe and North America. The disease is characterized by an increased thromboembolic risk, possibly caused by increased platelet counts. Furthermore, increased platelet function and/or increased platelet turnover may play a role. We aimed to explore: (1) whether platelet function and platelet turnover are increased in ET patients compared with healthy controls, and (2) whether these parameters are associated with increased thromboembolic risk and, therefore, may support decision-making on treatment in ET patients. We performed a systematic literature search on March 20, 2020 in Embase and PubMed following the Preferred Reporting Items for Systematic and Meta-Analysis (PRISMA) guidelines. In total, 1,923 articles were identified, 38 of which were included according to prespecified inclusion and exclusion criteria. Among the 38 studies, platelet activation (CD36 and CD62P) was investigated in 18 studies and was found to be increased in 12 of these. Platelet aggregation was investigated in 21 studies and was reported to be reduced in 20 of them. Platelet turnover (immature platelet count and mean platelet volume) was investigated in five studies with inconclusive results. No parameters were reported to predict the risk of thromboembolic events. In conclusion, platelet activation was increased in ET patients, but platelet aggregation was reduced. Future studies exploring markers of thromboembolic risk in ET patients are warranted.

Bidirectional relationship between atrial fibrillation and stroke.

The temporal relationship between atrial fibrillation (AF) and stroke has always been considered one-way: the presence of arrhythmia favors the occurrence of stroke. Recent studies have questioned this association and raised the possibility that it may be bidirectional. Some ischemic events are actually due to stasis following AF episodes. Others are caused by the same substrate, atrial cardiomyopathy, which can cause both AF and stroke. Arrhythmia would in turn be both a possible causal factor and a marker of thrombo-embolic risk. It is therefore essential, in addition to always looking for a possible AF after a stroke, using the new technologies of prolonged cardiac monitoring, to highlight, regardless of the history, the common risk factors, whose treatment can improve the prognosis, not only with respect to prevention of thrombo-embolisms but also of heart failure and mortality.

La fibrillation atriale : un facteur ou un marqueur du risque thromboembolique ? Du concept à la thérapie

The main complication of atrial fibrillation is stroke. Twenty years ago, the interest of vitamin K antagonist has been clearly demonstrated but these drugs are difficult to manage. For the last 10 years, direct oral anticoagulants have been developed. These drugs have demonstrated a non-inferiority as compared to vitamin K antagonist and a clear decrease in intra cerebral hemorrhages. Anticoagulation is indicated in a large majority of patients with atrial fibrillation. Nevertheless, many points remained questionable, like the anticoagulation of low risk patients, the choice of oral anticoagulants dosages, the anticoagulation according to the type of atrial fibrillation and the strategy in coronary artery disease patients for example. Recently it has been demonstrated that in many patients there were no temporal relationship between the occurrence of atrial fibrillation episodes and stroke. That means that in many cases atrial fibrillation is not the factor but the marker of thromboembolic risk.

Next generation sequencing to dissect the genetic architecture of KNG1 and F11 loci using factor XI levels as an intermediate phenotype of thrombosis.

Venous thromboembolism is a complex disease with a high heritability. There are significant associations among Factor XI (FXI) levels and SNPs in the KNG1 and F11 loci. Our aim was to identify the genetic variation of KNG1 and F11 that might account for the variability of FXI levels. The KNG1 and F11 loci were sequenced completely in 110 unrelated individuals from the GAIT-2 (Genetic Analysis of Idiopathic Thrombophilia 2) Project using Next Generation Sequencing on an Illumina MiSeq. The GAIT-2 Project is a study of 935 individuals in 35 extended Spanish families selected through a proband with idiopathic thrombophilia. Among the 110 individuals, a subset of 40 individuals was chosen as a discovery sample for identifying variants. A total of 762 genetic variants were detected. Several significant associations were established among common variants and low-frequency variants sets in KNG1 and F11 with FXI levels using the PLINK and SKAT packages. Among these associations, those of rs710446 and five low-frequency variant sets in KNG1 with FXI level variation were significant after multiple testing correction and permutation. Also, two putative pathogenic mutations related to high and low FXI levels were identified by data filtering and in silico predictions. This study of KNG1 and F11 loci should help to understand the connection between genotypic variation and variation in FXI levels. The functional genetic variants should be useful as markers of thromboembolic risk.

Markers of Thromboembolic Risk Were Insignificantly Affected By Either Intraosseous or Intravenous Idarucizumab in a Dabigatran-Anticoagulated Porcine Polytrauma Model

Introduction: Idarucizumab is a monoclonal humanized antibody fragment (Fab), designed to reverse dabigatran anticoagulation. It is approved for urgent reversal of dabigatran anticoagulant effects in massive bleeding or prior to urgent interventions. It is administered intravenously (i.v.), either as a bolus or a short infusion (2x2.5 g). In hemorrhagic shock gaining i.v. might be challenging, and alternative methods such as intraosseous (i.o.) administration are an alternative life-saving procedure. Due to the molecular size of idarucizumab (50 kDa), the efficacy and safety, including the passage from the i.o. compartment to circulation, are unknown. In this study we investigated the efficacy and the prothrombotic risk of idarucizumab, given i.v. and i.o. in a large animal polytrauma model.Methods: After ethical approval, 21 male pigs were administered oral dabigatran etexilate for 3 days (30 mg/kg twice daily). Following anesthesia, to achieve constant plasma levels, further dabigatran was infused on day 4 (0.77 mg/kg/h for 30 min plus 0.2 mg/kg/h for 60 min). Animals were randomized 1:1:1 to receive 1) i.o. placebo (control group), 2) i.o. idarucizumab (60 mg/kg), or 3) i.v. idarucizumab (60 mg/kg). The standardized polytrauma consisted of a blunt liver injury and a femur fracture. After trauma and hemorrhagic shock, animals were resuscitated with Ringer’s solution. Idarucizumab (i.o. or i.v.) or placebo (i.o.) were administered 15 min after trauma, either via an i.o. access (left tibial plateau, EZ-IO¨), or an i.v. access. Animals were observed up to 240 min after trauma, and total blood loss was assessed after the observation period or animal’s death. Coagulation variables included dabigatran plasma concentration, global coagulation assays (PT, aPTT) and thromboelastometry. For a differentiated risk assessment, thrombin generation and thrombin-antithrombin (TAT) levels, indicating the extent of coagulation activation, and D-Dimers, as markers of thromboembolic risk, were obtained. Hemodynamic monitoring comprised cardiac output, mean arterial and mean pulmonary arterial pressure. For statistical analysis, ANOVA (mean ± SD) and the log-rank test for survival were used.Results: Prior to trauma, all animals showed comparable plasma concentration of dabigatran (583 ± 139 ng/mL). Following idarucizumab administration, dabigatran plasma concentration was not detectable in both groups. Binding of dabigatran was associated with a normalization of whole blood and plasma coagulation variables. Total blood loss post-injury was comparable between both idarucizumab groups (i.o.: 1085 ± 102 mL, i.v.: 1142 ± 125 mL; P>0.05) with 100% survival. In contrast, control animals (no anticoagulation and no idarucizumab) exhibited the highest total blood loss, which was significantly higher than in idarucizumab treated pigs (4065 ± 557 mL, P<0.001). 6 out of 7 control animals died within the observation period (mean survival: 117 min; P<0.00001). Dabigatran concentration remained elevated throughout the observation period (last sampling point; mean: 302 ng/mL; range: 176-468 ng/mL). Thrombin generation after dabigatran infusion and trauma was not measurable. After idarucizumab, thrombin generation was restored close to baseline levels (Peak height: 128 ± 39 nM, ETP: 360 ± 106 nM*min) (both i.o. and i.v., P<0.05 vs. control). Likewise, only in idarucizumab groups TAT levels indicated re-appearance of activation of coagulation, as compared to the control group. However, there was no significant difference in D-dimers 60 min after trauma between all groups (i.o.: 1164 ± 553 ng/mL; i.v.: 1216 ± 520 ng/mL; control: 747 ± 572 ng/mL; P>0.05). Clinically no signs of thromboembolic adverse were observed.Conclusion: The route of application (i.o. or i.v.) of idarucizumab has no impact on the efficacy of the reversal of dabigatran. Despite the size of idarucizumab, therapy can be safely applied via an i.o. access. In patients with severe bleeding and hemorrhagic shock under dabigatran application, i.o. administration of idarucizumab is a safe alternative. [Display omitted] DisclosuresHonickel:Böhringer Ingelheim Pharma GmbH & Co KG: Other: travel support. ten Cate:Böhringer Ingelheim: Consultancy, Honoraria, Research Funding; CSL Behring: Research Funding; Stago: Consultancy; Bayer: Consultancy, Honoraria, Research Funding; Philips: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Leo Pharma: Consultancy, Honoraria. Rossaint:CSL Behring: Consultancy, Honoraria; Böhringer Ingelheim: Consultancy, Honoraria; Novo Nordisk: Consultancy, Honoraria. Grottke:Böringer Ingelheim: Consultancy, Honoraria, Research Funding; Novo Nordisk: Research Funding; Biotest: Research Funding; CSL Behring: Consultancy, Honoraria, Research Funding; Nycomed: Research Funding; Bayer: Consultancy, Honoraria; Octapharma: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Portola: Consultancy, Honoraria.

Erythrocytes and Platelets May Contribute to Hypercoagulability In Nephrotic Syndrome Through Enhanced Phosphatidylserine Exposure and Microparticles Release

Abstract 36 Background.Nephrotic syndrome (NS) is frequently accompanied by thromboembolic complications such as renal vein thrombosis, deep vein thrombosis and pulmonary embolism. However, the cause of the hypercoagulable state in NS patients is not understood. In contrast to quiescent cells, membrane-derived microparticles have exposed phosphatidylserine which may support procoagulant enzyme complexes in thrombosis. Objectives.The aim of this work was to measure the type and quantity of MPs that expose PS in NS patients, and to evaluate the associated procoagulant activity (PCA). Methods.The subjects with membranous nephropathy (MN) or minimal change nephrotic syndrome (MCNS) were compared to healthy controls. Flow cytometry and confocal microscopy was used to evaluate microparticles. PCA was determined by clotting time and purified coagulation complex assays. Results.We found that the number of lactadherin+ MPs was significantly higher in each NS group MCNS (3230 ± 536)/MN (4642 ± 697) than that in the controls (1748 ± 239), furthermore, MPs in MN patients are significantly higher than ones in MCNS (P < 0.05; Table 1), which mostly derived from RBC and platelet membranes. The percentage of lactadherin+ RBCs was also significantly increased in each NS group, MN (9.7 ± 3.2%)/MCNS (5.1 ± 2.4%) patients compared to the controls (0.5 ± 0.2%). In addition, the mean percentage of lactadherin+ RBCs in MN showed significantly higher than that in MCNS (P < 0.05). In both NS groups, the percentage of lactadherin+ platelets was significantly higher than that in healthy control subjects (4.1 ± 1.1%) (P < 0.05 for both). Furthermore, patients in MN (11.5 ± 3.1%) also had significantly increased lactadherin+ platelets than in MCNS (7.3 ± 2.3%) (P < 0.05). By confocal laser-scanning microscope, nearly no staining by Alexa Fluro 488-lactadherin could be detected on RBCs or platelets membranes in healthy subjects, whereas a light green fluorescence on RBC and platelet with lactadherin accompanying vesiculation were observed in NS patients. PCA of RBCs/platelets from healthy individuals and NS patients was assessed by recalcification time assays, intrinsic, extrinsic FXa and prothrombinase assays. MPs shedding and PS exposure of RBCs/platelets were highly procoagulant in NS patients and blockade of PS with lactadherin inhibited over 90% of PCA. However, an anti-TF antibody had no significant inhibition effect (Figure 1). [Display omitted] Table 1MPs numbers per microliter of plasma in MCNS, MN and controls.ControlsMCNSMNTotal lactadherin+ MPs (/μl)1748 (1341–2014)3230* (2484–3819)4642*,# (3499–5496)Lactadherin+ CD41a+1237 (944–1450)2363* (1888–2587)3470*,# (2587–4144)Lactadherin+ CD235a+23 (16–32)174* (138–205)335*,# (262–410)Lactadherin+ CD142+2.6 (0–4.2)2.7 (0–4.9)2.6 (0–6.8)Corrected for the number of events with isotype controls,*P < 0.05 versus controls.#P < 0.05 versus MCNS. Conclusions.This is the first study to show that loss of RBCs/platelets membrane phospholipid asymmetry with increased PS exposure and MPs release may contribute to the hypercoagulable state of NS patients. The extent of PS exposure on cells and MPs may be a marker of thromboembolic risk in these patients. Disclosures:No relevant conflicts of interest to declare.

Usefulness of Left Atrial Volume Versus Diameter to Assess Thromboembolic Risk in Mitral Stenosis

In patients with mitral stenosis (MS) in sinus rhythm (SR), guidelines recommend anticoagulation if the left atrium is enlarged based on diameter measurements. We sought to compare the association of left atrial (LA) diameter and LA volume with markers of thromboembolic risk (peak LA appendage emptying velocity [LAAv] and LA spontaneous contrast density) measured during transesophageal echocardiography in 152 patients with moderate to severe MS. High thromboembolic risk was defined by a peak LAAv < 25 cm/s and/or dense spontaneous contrast. Mean LA diameter (50 ± 7 mm, 32 to 77) and LA volume (152 ± 70 ml, 67 to 720) were significantly correlated (r = 0.71, p < 0.0001), but the relation was curvilinear and the 95% confidence interval increased with LA diameter. In the subset of 80 patients in SR who underwent clinically indicated transesophageal echocardiography, body surface area (BSA)-indexed LA volume but not LA diameter differentiated patients with normal from those with low LAAv (86 ± 17 vs 71 ± 17 ml/m(2), p < 0.01, and 50 ± 6 vs 48 ± 6 mm, p = 0.13, respectively) and patients with dense spontaneous contrast from those with no or mild spontaneous contrast (81 ± 16 vs 63 ± 15 ml/m(2), p < 0.01, and 49 ± 6 vs 46 ± 5 mm, p = 0.11, respectively). BSA-indexed LA volume provided the highest area under the curve (0.85) for high thromboembolic risk and LA diameter the lowest (0.65). A BSA-indexed LA volume > 60 ml/m(2) provided an excellent 90% sensitivity despite 44% specificity, 76% positive predictive value, and 70% negative predictive value. Use of this threshold instead of 50 or 55 mm would have changed the indication for anticoagulation in 51% to 77% of patients. In conclusion, LA volume was more strongly associated with markers of thromboembolic risk than LA diameter, which poorly reflected LA size. Our results support the use of BSA-indexed LA volume to guide the decision for anticoagulation in patients with MS in SR, which may lead to significant change in the management of those patients. We suggest a threshold of 60 ml/m(2), which has good sensitivity, albeit with low specificity.

PO-68 TEG: a potential marker of thromboembolic risk in cancer patients?

PO-68 TEG: a potential marker of thromboembolic risk in cancer patients?

465 Relationship between inflammatory status and markers of thromboembolic risk on transesophageal echocardiography in patients with atrial fibrillation

Eur J Echocardiography Abstracts Supplement, December 2006 Background: The prevalence and clinical significance of atherosclerotic aortic disease has now been documented in a variety of patient populations by use of transesophageal echocardiography (TEE). The use of standardised and automatic software for measurement of intima-media thickness (IMT) could be useful in daily practice. Aim: To evaluate a new parametric quantification software used in digitalised TEE aortic images. Methods: The QLA 2.0 ® (Philips) allows detection of the borders from different structures and selecting a region of interest analysis (ROI) is able to determine the anatomic interface between intima and media. The study population comprised 31 consecutive patients (62±16 years) referred for TEE. The images of the aortic arch (Aa) (0ae) and the descendent aorta (dA) (90ae) were digitalised and saved. The offline analyses were made with the QLAB software version 2.0 ®. We used two ROI (10 and 20 mm) to automatically define the IMT. When the optimal image definition was less than 80% (value determined by the software), we proceeded with visual determination of the IMT. Results: The medium IMT determined in the Aa with a 10 mm ROI was 1.76±1.04 mm, with a medium optimal image definition of 85% (17 determined automatically, 14 determined visually). At the same level the medium IMT with a 20 mm ROI was 1.81±0.88 mm, with a medium optimal image definition of 86% (12 determined automatically, 18 determined visually). The medium IMT determined in the dA with a 10 mm ROI was 1.88±1.23 mm, with a medium optimal image definition of 92% (19 determined automatically, 11 determined visually). At the same level the medium IMT with a 20 mm ROI was 1.84±1.19 mm, with a medium optimal image definition of 89% (18 determined automatically, 11 determined visually). We were not able to measure four IMT (one with 20 mm ROI at aortic arch level and one with 10 mm ROI and two with 20 mm ROI at the descendent aorta level) because of deficient intima-media interface definition. Conclusion: The QLAB version 2.0 ® software can be used in TEE images to determine the IMT of the Aa and the dA. The automatic IMT assessment was more feasible at the descendent aorta.

Inflammation and markers of thromboembolic risk on transoesophageal echocardiography in atrial fibrillation

Inflammation and markers of thromboembolic risk on transoesophageal echocardiography in atrial fibrillation

Case-control Study of the Frequency of Thrombophilic Disorders in Couples with Late Foetal Loss and no Thrombotic Antecedent

Women with familial thrombophilia have an increased risk of still birth. We postulated that the presence of asymptomatic risk factors for venous thrombosis might be a risk factor for late foetal loss. We performed a case-control study on the prevalence of heritable thrombophilic defects, of antiphospholipid-related markers and of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with at least one episode of late unexplained foetal loss and in control women with successful pregnancies. Partners of cases and controls were also studied. Written conclusions of the pathological examination of the placentas, when available, were also reviewed. We found at least one positive biological risk factor for venous thrombosis in 21.1% of the patients and in 3.9% of the controls (p < 10(-4)). In women, the crude odds ratio for still birth associated with any positive biological risk factor for venous thrombosis was 5.5, 95% confidence interval (95%CI) [3.4-9.0]. No difference was found between partners of cases and controls (5.2% and 4.7%). Using conditional logistic regression analysis, 4 adjusted risk factors for still birth remained: protein S deficiency, positive anti beta2 glycoprotein I IgG antibodies, positive anticardiolipin IgG antibodies and the factor V Leiden mutation. The C677T mutation in the MTHFR gene was not an individual risk factor but an homozygous genotype was strongly associated with the former 4 risk factors (16.8% of patients vs. 0.9% of controls). In women with such associations, still births always occurred in absence of folic acid supplementation during pregnancy. Available conclusions of pathological analysis of placentas were found to have a very high proportion of "maternal vascular disease of the placenta" in patients with at least one positive risk marker for thromboembolism, specially in case of association with the C677T MTHFR homozygous genotype, compared to patients with negative markers (p <10(-4)). Late foetal loss, through placenta thrombosis, may sometimes be the consequence of a maternal multifactorial prothrombotic state associating traditional heritable or acquired thrombosis risk factors to conditions predisposing to an acute mild hyperhomocysteinaemia (coexistence of a genetic predisposition with late pregnancy-related increased folate needs).

Prophylaxis of thromboembolic events in congestive heart failure.

In patients with heart failure the incidence of thromboembolism is 0.9-5.5%/year (mean 1.9%/year), but no randomized studies are available to support the indication for anticoagulant therapy in those patients. Atrial fibrillation and previous thromboembolic events seem to be the major risk factors, whereas the effect of ventricular dysfunction has not been independently evaluated; nonetheless several studies suggest that thromboembolism is more likely among those patients with lower ejection fraction and lower peak exercise oxygen consumption. Anticoagulant therapy seems to be indicated also in patients with left ventricular aneurysm with mobile and protruding thrombi. Several studies of patients with dilated cardiomyopathy show that the incidence of thromboembolism ranges from 1.6 to 4.5%/year in patients not treated with anticoagulants, while it is virtually absent in anticoagulated patients. The clinical opportunity of long-term anticoagulant treatment in heart failure patients should be weighted not only on the clinical markers of thromboembolic risk, but also on the relative risk/benefit ratio of the single patient.

Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast and thromboembolic risk in vivo

Objectives. The aim of this study was to determine the relations between spontaneous echo contrast, left atrial appendage blood flow velocity and thromboembolism.Background. Left atrial thrombus and spontaneous echo contrast, a putative marker of thromboembolic risk, are frequently located in the left atrial appendage. Measurement of left atrial appendage outflow Doppler velocity by transesophageal echocardiography is a recent technique for assessment of left atrial appendage function, which may be important in thrombus formation.Methods. Transthoracic and transesophageal echocardiographic studies were performed in 140 patients with atrial fibrillation (chronic in 80 patients, paroxysmal in 50 patients, first episode <2 weeks in 10 patients). The left atrium and appendage were inspected for thrombus and spontaneous echo contrast, which was graded from 0 (none) to 4+ (severe). Outflow velocity profiles were obtained by pulsed wave Doppler at the orifice of the left atrial appendage.Results. Left atrial spontaneous echo contrast was present in 78 patients (56%). In multivariate logistic regression analysis, spontaneous echo contrast was the only significant correlate of left atrial thrombus and was present in 14 (93%) of 15 patients. Spontaneous echo contrast and age were associated positively, and anticoagulant therapy was associated negatively, with previous thromboembolic events. Increasing grades of spontaneous echo contrast were associated with decreasing left atrial appendage blood velocity. The velocity in patients with thrombus was not significantly different from that in patients with 4+ spontaneous echo contrast. In multivariate linear regression analysis, the grade of spontaneous echo contrast was significantly and negatively associated with left atrial appendage velocity (p = −0.0001) and mitral regurgitation (p = −0.0002) and significantly and positively associated with left atrial area (p = 0.0005). The odds ratio for spontaneous echo contrast was 28:1 for low left atrial appendage blood flow velocity (<35 cm/s) and 96:1 for low velocity and the absence of mitral regurgitation.Conclusions. Spontaneous echo contrast is the cardiac factor most strongly associated with left atrial appendage thrombus and embolic events. Spontaneous echo contrast formation is promoted by reduced blood flow velocity and increased left atrial size but is diminished by mitral regurgitation.

Left atrial spontaneous contrast echoes--markers of thromboembolic risk in patients with atrial fibrillation.

A consecutive series of 80 patients with atrial fibrillation were studied with both precordial and transoesophageal echocardiography. Left atrial spontaneous contrast echoes were observed in one patient with precordial echocardiography and in 26 patients (33%) with transoesophageal echocardiography. They were found most commonly in patients with rheumatic mitral valve disease (67%) but were observed in 28% of patients with lone atrial fibrillation. Their presence was unrelated to the age, gender and therapy of the patient. Although they were more common in patients with a large left atrium, they were sometimes observed in a normal sized atrial chamber. They were more common in chronic (40%) than in paroxysmal atrial fibrillation (5.6%). No patient had severe mitral regurgitation, but contrast echoes were observed in some patients with mild or moderate mitral regurgitation. Of the 26 patients with spontaneous contrast echoes, six (23%) had echoes consistent with left atrial thrombus compared to one of the 54 patients without these echoes (1.9%) (P = 0.006); 17 (65%) had suffered a previous thromboembolic event compared to 17 of the 54 without these echoes (32%) (P = 0.009). These data support the concept that spontaneous contrast echoes in the left atrium are associated with sluggish blood flow and a thrombogenic environment. Transoesophageal echocardiography may thus be useful in assessing which patients with atrial fibrillation might most benefit from anticoagulation. This hypothesis needs to be evaluated further in a prospective study.