Left atrial thrombus and systemic embolism in patients with mitral valve disease is common, with a reported incidence of between 12% and 17%, especially if the patient is not anticoagulated and if atrial fibrilla- tion (AF) is present. 1-4 Nevertheless, the precise patho- physiologic mechanisms leading to thrombogenesis (thrombus formation) in these patients have not been fully elucidated. Recent progress in the field of vascular biology has generated important insights into factors that both maintain the normal vasculature and play important roles in the processes of thrombogenesis. For example, From the a Haemostasis, Thrombosis, and Vascular Biology Unit, University Depart- ment of Medicine, City Hospital; the b Department of Cardiothoracic Surgery, Wals- grave Hospital; and the c Department of Biological Sciences, Manchester Metropoli- tan University. Ira Goldsmith was supported by a nonpromotional project grant from Sorin Biomed- ica SpA, Saluggia, Italy. Submitted October 28, 1999; accepted July 14, 2000. Reprint requests: Dr G.Y.H. Lip, Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Dudley Road, Birmingham, B18 7QH, UK. E-mail: G.Y.H. Lip@bham.ac.uk Copyright © 2000 by Mosby, Inc. 0002-8703/2000/$12.00 + 0 4/1/110284 doi:10.1067/mhj.2000.110284 Valvular and Congenital Heart Disease Atrial endocardial changes in mitral valve disease: A scanning electron microscopy study Ira Goldsmith, FRCS(Ed), FRCS(Glas), a,b Patricia Kumar, PhD, c Peter Carter, BSc, c Andrew D. Blann, PhD, MR Path, a Ramesh L. Patel, MD, FRCS(Ed), FRCS CTh, b and Gregory Y. H. Lip, MD, FRCP(Ed), FACC, FESC a Birmingham, Coventry, and Manchester, UK Background The precise contribution of left atrial appendage (LAA) endocardial damage and dysfunction to the process of thrombus formation in patients with mitral valve (MV) disease, especially in the presence of atrial fibrillation (AF), has not as yet been clearly described. This may be important because the LAA is the usual site for thrombus formation. Methods The purpose of this study was to describe endocardial surface changes, through the use of scanning electron microscopy, in the left and right atrial appendages of patients with MV disease and the differences, if any, between patients with mitral stenosis and mitral regurgitation as well as between those with AF and sinus rhythm. Our second objective was to relate endocardial changes to plasma levels of von Willebrand factor (vWf), an established marker for endothelial damage. LAA specimens were obtained immediately after commencement of cardiopulmonary bypass from 35 patients (18 men; mean age 65 years, range 20 to 85) during surgery for MV repair or replacement. Right atrial appendage (RAA) speci- mens were similarly obtained as controls for individual patients. The specimens were fixed in 2.5% glutaraldehyde solution overnight, stored in Sorensen’s phosphate buffer, and examined by means of scanning electron microscopy. Two indepen- dent observers documented the most advanced lesion in each specimen as follows: (1) “minimal” changes, with minimal dis- ruption of the endocardium; (2) “intermediate” changes or prethrombotic lesions; and (3) “advanced” changes, with endo- cardial disruption and thrombotic lesions. Plasma levels of vWf were also measured (enzyme-linked immunosorbent assay) in all patients, and results were compared with those of age- and sex-matched healthy control patients. Results Advanced changes were more frequently seen in the endocardium of the LAA when compared with the RAA (31% vs 6%), whereas minimal changes were more frequently seen in the RAA compared with the LAA (23% vs 6%) (P = .00167). Similarly, the LAA from patients with mitral stenosis had a higher proportion of “advanced” endocardial changes when compared with patients with mitral regurgitation (67% vs 24%; P = .0066). The LAA in patients with AF had more “advanced” changes (39% vs 27%), but this was not statistically significant. Plasma vWf levels were significantly higher in patients with MV disease compared with healthy control patients (132 ± 33 IU/dL vs 99 ± 37 IU/dL; P = .0004) and in patients with advanced LAA changes compared with earlier changes (149 ± 34 IU/dL vs 121 ± 31 IU/dL; P = .042). Conclusions Endocardial damage occurs in the atrial appendages of patients with MV disease. Potentially thrombo- genic changes are more commonly seen in the LAA compared with the RAA and in patients with mitral stenosis compared with mitral regurgitation. These anatomic appearances may contribute to the risk of intra-atrial thrombus formation in patients with mitral valve disease, especially if AF is present. (Am Heart J 2000;140:777-84.)