Refining the Prothrombotic State and Prognosis in Atrial Fibrillation With Left Atrial Appendage 3D Echocardiography

BACKGROUND Left atrial (LA) volume is an echocardiographic marker of remodeling, thromboembolic risk, and prognosis in atrial fibrillation (AF); limited data are available on LA appendage (LAA) characterization beyond morphology. We sought to evaluate LAA characteristics in 2-dimensional (2D) and 3-dimensional (3D) transesophageal echocardiography (TEE) and the correlation with LA/LAA prothrombotic state and prognosis. METHODS We prospectively studied 206 hospitalized patients with AF using 2D transthoracic echocardiography (TTE) and 2D/3D TEE of the LAA ≤24 hours from admission. Patients were divided according to the presence or absence of LAA sludge and/or thrombus. Data on clinical events were collected for 2 years. RESULTS Patients with LAA sludge/thrombus (n=35) on admission had higher LA volumes, lower left ventricular ejection fraction, lower LAA emptying and filling flow velocity, larger 2D LAA measurements (2D LAA ostium diameter, 2D LAA area) as well as larger 3D LAA measurements (higher 3D LAA volumes (LAAV), higher 3D end-systolic [ES] LAA ostium area), and more frequently non-chicken wing morphology. On multivariable logistic regression analysis, LAA filling flow velocity and 3D ES LAAV were associated with the presence of LAA sludge/thrombus at admission ( P =0.031 and P <0.0001 respectively). Receiver operating characteristic curve analysis revealed the optimal cut-off for 3D ES LAAV to discriminate patients at risk of death within 2 years was 9.3 mL. Kaplan–Meier curves demonstrated a significant difference in survival at 2-year follow-up according to this value: 3 deaths occurred in the group with 3D ES LAAV <9.3mL and 11 in those with volume ≥9.3 mL ( P =0.02). CONCLUSIONS 3D characterization of LAAV depicts a degree of LAA remodeling in AF that appears associated with LA/LAA thrombogenicity and mid-term prognosis. CONDENSED ABSTRACT Limited data are available on left atrial appendage (LAA) remodeling in atrial fibrillation (AF). We hypothesized that 3-dimensional (3D) evaluation of the LAA volume in AF could help to refine the prothrombotic state and prognosis in AF. Patients with LAA sludge and/or thrombus exhibited lower LAA filling and emptying flow velocities, and higher 2-dimensional (2D) and 3D LAA measurements. On multivariable analysis, LAA filling flow velocity and 3D end-systolic LAA volume were associated with the presence of LAA sludge/thrombus at admission (respectively, P =0.031 and P <0.0001). Kaplan–Meier curves demonstrated a significant difference in survival at 2 years according to 3D ES LAA volume ( P =0.02). Three dimensional LAA volume reflects the degree of LAA remodeling in AF and is associated with prothrombotic state and prognosis. ### Competing Interest Statement Dr Cohen reports research grants from RESICARD (research nurses) and the companies ARS, Bayer and Boehringer-Ingelheim; and consultant and lecture fees from AstraZeneca, Bayer Pharma, BMS-Pfizer Alliance, Boehringer-Ingelheim, Daiichi Sankyo and Novartis, unrelated to the present work. The other authors declare that they have no competing interest. ### Clinical Trial NCT02741349 ### Funding Statement This work was partially funded by Bayer and the Fondation de France. Dr. Soulat-Dufour has received a grant from Fédération Française de Cardiologie. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee authorization: CPP Ile de France V, number: 2014-A00280-47. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data referred to the mauscript are available * 2D : 2-dimensional 3D : 3-dimensional AF : atrial fibrillation BNP : B-type natriuretic peptide CRP : C-reactive protein ED : end-diastole ES : end-systole I : indexed LAA : left atrial appendage LAAV : left atrial appendage volume TEE : transesophageal echocardiography TTE : transthoracic echocardiography