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

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 CHA2DS2-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.

Prediction of Left and Right Atrials Appendage Thrombosis in Patient with Non-Valvular Atrial Fibrillation

“…Кроме того, известны гены, влияющие на кардиогенез (GATA4, GATA5, GATA6, GREM2, NKX2-5, NKX2-6), клеточную архитектонику и межклеточное взаимодействие (GJA1, GJA5, LMNA, NUP155), мутации, ассоциированы с развитием РП и ФП [32]. В исследовании Springer A. et al (2021) изучались генетические предикторы ТЭ осложнений на фоне ФП [33]. Наличие Tyr2561 варианта vWF (фактор фон Виллебранда) у пациентов младше 65 лет чаще встречалось при наличии тромбоза уЛП (27% в группе тромбоза уЛП против 7% в группе отсутствия тромбоза уЛП, P=0,066), в то время как мутации FVL (фактор V Лейдена), протромбина встречались с одинаковой частотой в обеих группах [33].…”

“…В исследовании Springer A. et al (2021) изучались генетические предикторы ТЭ осложнений на фоне ФП [33]. Наличие Tyr2561 варианта vWF (фактор фон Виллебранда) у пациентов младше 65 лет чаще встречалось при наличии тромбоза уЛП (27% в группе тромбоза уЛП против 7% в группе отсутствия тромбоза уЛП, P=0,066), в то время как мутации FVL (фактор V Лейдена), протромбина встречались с одинаковой частотой в обеих группах [33]. В работе Gokce M. et al (2003) также было показано отсутствие предиктивной ценности мутации FVL в отношении тромбоза уЛП [34].…”

Treatment of Persistent Left Atrial Appendage Thrombus in Patients with Atrial Fibrillation on Adequate Oral Anticoagulation: Pathways of Care for All-comers and Heart Failure Patients

“…Despite anticoagulant therapy, similar findings were reported elsewhere, confirming the association of high CHA 2 DS 2 -VASc score and LAT presence and its link to future cerebrovascular events. 19,20 However, this relationship is not that simple because even in patients with non-valvular AF and low CHA 2 DS 2 -VASc score, elevated plasma homocysteine levels were predictive of LA/LAA thrombus. 21 Similarly, in two Polish cohorts enrolling consecutive AF patients of whom the majority or all were receiving oral anticoagulation, the presence of LA/LAA thrombus was 5.7% and 7.5%, respectively, while persistent and permanent AF, renal dysfunction (estimated glomerular filtration rate <56 ml/min/1.73m 2 ), lower mean LAA flow velocity and history of vascular disease were established as solid independent predictors of LA/LAA thrombus formation.…”