Correlation between quantitative left atrial spontaneous echocardiographic contrast and intact fibrinogen levels in mitral stenosis

LETTER TO THE EDITOR

Correlation Between Quantitative Left Atrial Spontaneous Echocardiographic Contrast and Intact Fibrinogen Levels in Mitral Stenosis To the Editor: The aim of a recently published study by Wang et al (J Am Soc Echocardiogr 2001;14:285-91) was to evaluate the relation between left atrial spontaneous echo contrast (LASEC) and coagulation activity. The conclusions of this study were that LASEC severity was positively correlated with levels of intact fibrinogen, but that there was no relationship between LASEC severity and left atrial markers of thrombin generation and activity. Although the importance of defining the relationship between LASEC and coagulation activity is not in question, we have significant concerns about 3 areas in the study. First, the relation between coagulation activity and LASEC in mitral stenosis has been addressed in a number of previously published studies that were not cited by Wang et al. In 1996, we measured left atrial and peripheral venous levels of prothrombin fragment 1+2 (F1+2), a marker of thrombin generation, in 32 patients with mitral stenosis.1 The left atrial level of F1+2 exceeded the peripheral venous level, suggesting that there was an increase in thrombin generation in the left atrium. However, although this increase was evident in patients with LASEC and either sinus rhythm or atrial fibrillation, it was not evident in patients without LASEC. Furthermore, the only independent predictor of the presence of increased left atrial thrombin generation was the presence of LASEC.1 Subsequently, Zaki et al2 measured right and left atrial levels of thrombin antithrombin complex (TAT), also a marker of thrombin generation, and reported not only that the left atrial level exceeded the right atrial level, but that the only significant predictor of an increased left atrial TAT level was LASEC. Two other studies in mitral stenosis have also reported that LASEC is a predictor of increases in systemic levels of markers of thrombin generation.3,4 Second, there are numerous inconsistencies in the coagulation marker data of Wang et al that have not been discussed.Thus, D-dimer levels were significantly elevated in some patients but undetectable in others.There was also a lack of any relation between right atrial and left atrial levels of D-dimer within patients, even though previous studies have found D-dimer levels to be similar in the left atrium, right atrium, and peripheral vein in mitral stenosis.1,5 In addition, although right atrial levels of TAT were undetectable in more than half the patients, previous studies have

shown that systemic levels of TAT are elevated in mitral stenosis.2-4 Finally, the finding that TAT levels were higher in the left than right atrium but that F1+2 levels were similar in the 2 atria is not in accord with the notion that both markers are measures of thrombin generation, or the observation that left atrial levels of both markers were elevated in a previous study in mitral stenosis.6 An explanation of all these inconsistencies is not readily apparent, but their presence clearly raises concerns about the quality of the coagulation data presented in the study of Wang et al. Lastly, only 11 subjects were included in the study of Wang et al and only 2 of these did not have LASEC. Because of the small patient numbers, the lack of relation between LASEC and coagulation activity in this study could thus easily have been a false-negative result. Roger E Peverill MB, BS, PhD Joseph Smolich MB,BS, PhD Centre for Heart and Chest Research Department of Medicine Monash Medical Centre and Monash University 246 Clayton Rd, Clayton, 3168 Victoria, Australia 27/8/118034

REFERENCES 1. Peverill RE, Harper RW, Gelman J, Gan TE, Harris G, Smolich JJ. Determinants of increased regional left atrial coagulation activity in patients with mitral stenosis. Circulation 1996;94:331-9. 2. Zaki A, Salama M, El Masry M, Abou-Freikha M, AbouAmmo D, Sweelum M, et al. Immediate effect of balloon valvuloplasty on hemostatic changes in mitral stenosis. Am J Cardiol 2000;85:370-5. 3. Buyukasik Y, Ileri M, Ozcebe OI, Haznedaroglu IC, Yetkin E, Kirazli S, et al. Increased systemic coagulation activity in patients with rheumatic mitral stenosis: assessment of the clinical and echocardiographic determinants. Blood Coagul Fibrinolysis 1999;10:417-21. 4. Ileri M, Buyukasik Y, Ileri NS, Haznedaroglu lC, Goksel S, Kirazli S, et al. Activation of blood coagulation in patients with mitral stenosis and sinus rhythm. Am J Cardiol 1998;81:795-7. 5. Yamamoto K, Ikeda U, Seino Y, Mito H, Fujikawa H, Sekiguchi H, et al. Coagulation activity is increased in the left atrium of patients with mitral stenosis. J Am Coll Cardiol 1995;25:107-12. 6. Yamamoto K, Ikeda U, Minezaki KK, Fukazawa H, Mizuno O, Kim S, et al. Effect of mitral valvuloplasty in mitral stenosis on coagulation activity. Am J Cardiol 1997;79:1131-5. doi:10.1067/mje.2002.118034

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