Genetic and Clinical Predictors of Left Atrial Thrombus: A Single Center Case-Control Study

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Abstract

Left atrial (LA) thrombus formation is the presumed origin of thromboembolic complications in patients with atrial fibrillation (AF). Beyond clinical risk factors, the factors causing formation of LA thrombi are not well known. In this case-control study, we analyzed clinical characteristics and genetic thrombophilia markers (factor V Leiden (FVL), prothrombin G20210A (FIIV), Tyr2561 variant of von Willebrand factor (VWF-V)) in 42 patients with AF and LA thrombus (LAT) and in 68 control patients with AF without LAT (CTR). Patients with LAT had more clinical conditions predisposing to stroke (mean CHA ₂DS ₂-VASc-score 3.4 ± 1.5 vs. 1.9 ± 1.4; P < 0.001), a higher LA volume (96 ± 32 vs. 76 ± 21 ml, P = 0.002) and lower LA appendage emptying velocity (0.21 ± 0.11vs. 0.43 ± 0.19 m/s, P < 0.001). Prevalence of FVL, FIIV and VWF-V mutations was not different, but in the subgroup of patients <65 years (y) there was a tendency for a higher incidence of VWF-V with a prevalence of 27% (LAT <65 y) vs. 7% (CTR <65 y, P = 0.066). These findings warrant further investigation of the VWF-V as a risk factor for LA thrombogenesis in younger patients.

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Most cited references 28

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2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS.

Paulus Kirchhof, Stefano Benussi, Dipak Kotecha … (2016)

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Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials.

Christian Ruff, Robert Giugliano, Eugene Braunwald … (2014)

Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes. We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71,683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045). This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population. None. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study

Jonas Olesen, Gregory Y. H. Lip, Morten Lock Hansen … (2011)

Objectives To evaluate the individual risk factors composing the CHADS2 (Congestive heart failure, Hypertension, Age≥75 years, Diabetes, previous Stroke) score and the CHA2DS2-VASc (CHA2DS2-Vascular disease, Age 65-74 years, Sex category) score and to calculate the capability of the schemes to predict thromboembolism. Design Registry based cohort study. Setting Nationwide data on patients admitted to hospital with atrial fibrillation. Population All patients with atrial fibrillation not treated with vitamin K antagonists in Denmark in the period 1997-2006. Main outcome measures Stroke and thromboembolism. Results Of 121 280 patients with non-valvular atrial fibrillation, 73 538 (60.6%) fulfilled the study inclusion criteria. In patients at “low risk” (score=0), the rate of thromboembolism per 100 person years was 1.67 (95% confidence interval 1.47 to 1.89) with CHADS2 and 0.78 (0.58 to 1.04) with CHA2DS2-VASc at one year’s follow-up. In patients at “intermediate risk” (score=1), this rate was 4.75 (4.45 to 5.07) with CHADS2 and 2.01 (1.70 to 2.36) with CHA2DS2-VASc. The rate of thromboembolism depended on the individual risk factors composing the scores, and both schemes underestimated the risk associated with previous thromboembolic events. When patients were categorised into low, intermediate, and high risk groups, C statistics at 10 years’ follow-up were 0.812 (0.796 to 0.827) with CHADS2 and 0.888 (0.875 to 0.900) with CHA2DS2-VASc. Conclusions The risk associated with a specific risk stratification score depended on the risk factors composing the score. CHA2DS2-VASc performed better than CHADS2 in predicting patients at high risk, and those categorised as low risk by CHA2DS2-VASc were truly at low risk for thromboembolism.

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Author and article information

Journal

Journal ID (nlm-ta): Clin Appl Thromb Hemost

Journal ID (iso-abbrev): Clin Appl Thromb Hemost

Journal ID (publisher-id): CAT

Journal ID (hwp): spcat

Title: Clinical and Applied Thrombosis/Hemostasis

Publisher: SAGE Publications (Sage CA: Los Angeles, CA )

ISSN (Print): 1076-0296

ISSN (Electronic): 1938-2723

Publication date (Electronic): 29 June 2021

Publication date Collection: Jan-Dec 2021

Volume: 27

Electronic Location Identifier: 10760296211021171

Affiliations

[1 ]Department of Cardiology, University Heart and Vascular Center, Hamburg, Germany

[2 ]Asklepios Hospital St. Georg, Hamburg, Germany

[3 ]Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[4 ]Asklepios Hospital Harburg, Hamburg, Germany

[5 ]DZHK, partner Site Hamburg/Kiel/Lübeck, Germany

[6 ]Division of Cardiology, Cardiac Neuro- and Electrophysiology Research Consortium (cNEP), EVK, Düsseldorf, Germany

[7 ]Department of Oncology and Hematology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

[8 ]Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK

Author notes

[*]Marc D. Lemoine, Department of Cardiology, University Heart and Vascular Center (UKE), Hamburg, Martinistraße 52, Hamburg 20246, Germany. Email: m.lemoine@ 123456uke.de

Author information

Marc D. Lemoine https://orcid.org/0000-0002-3799-7962

Article

Publisher ID: 10.1177_10760296211021171

DOI: 10.1177/10760296211021171

PMC ID: 8246465

PubMed ID: 34184557

SO-VID: f229cca4-e627-4260-9d82-a760394096b7

License:

This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date received : 28 February 2021

Date revision received : 29 April 2021

Date accepted : 11 May 2021

Custom metadata

cover-date January-December 2021

typesetter ts3

Keywords: atrial fibrillation,echocardiography,biomarkers,genetic association studies,left atrial thrombus,von willebrand factor,transesophageal echocardiography

Data availability:

Keywords: atrial fibrillation, echocardiography, biomarkers, genetic association studies, left atrial thrombus, von willebrand factor, transesophageal echocardiography

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