Correlates of spontaneous echo contrast in patients with mitral stenosis and normal sinus rhythm

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13. Walter SD, Feinstein AR, Wells CK. A comparison of multivariable mathematical methods for predicting survival-II. Statistical selection of nrognostic variables. J Clin Epidemiol 1990;43:349-59. - 14. Wells CK, Feinstein AR, Walter SD. A comparison of multivariable mathematical methods for nredictine survival-III. Accuracy of predictions in generating and challenge sets. J Clin Epidemiol 1990;43:361-72. 15. Detrano R, Lyons KP, Marcondes G, Abbassi N, Froelicher VF, Janosi A. Methodological problems in exercise testing research. Are we solving them? Arch Intern Med 1988;148:128995.

16. Hlatky M, Botvinick E, Brundage B. Diagnostic accuracy of cardiologists compared with probability calculations using Bayes’ rule. Am J Cardiol 1982;49:1927-31. 17. Detrano R, Janosi A, Lyons KP, Marcondes G, Abbassi N, Froelicher VF. Factors affecting sensitivity and specificity of a diagnostic test: the exercise thallium scintigram. Am J Med 1988;84:699-710. 18. Schwartz RS, Jackson WG, Celio PV, Richardson LA, Hickscintigraphy man JR Jr. Accuracy of exercise zolTl myocardial in asymptomatic young men. Circulation 1993;87:165-72.

Correkttes of spontaneous echo contrast in patients with mitral stenosis and normal sinus rhythm The purpose of this study was to evaluate the correlates of spontaneous echo contrast in mitral stenosis and normal sinus rhythm. Spontaneous echo contrast is associated with clot formation and embotic phenomena. It has been noted in conditions involving blood stasis, especially mitral stenosis and atrial fibrillation, but the correlates of spontaneous echo contrast in patients with mitral stenosis and normal sfnus rhythm have not been extensively evaluated. The tmnsthomcic and tmnsesophageal echocardllmms and clinical findings of 47 patients with mitral stenosis and normal sinus rhythm were reviewed. Left atrial size, mean tmnsmitml gradient, and valve area were measured, and the presence or absence of spontaneous echo contrast in the left atrium was noted. Spontaneous echo contrast was found in the echocardiogmms of 21 (45%, group 1) of 47 patients. There was no contrast in those of the other 26 patients (group 2). Mean tmnsmitml grrdient was significantly higher in group 1 (13.6 + 5.2 mm Hg) than in group 2 (10.5 t 4.9 mm Hg) @ < 0.05). Mitral valve ama was significantly smalfer in group 1 than in group 2 (1.0 t 0.5 vs 1.4 + 0.5 cm2; p < 0.02). There was a trend toward a h&her prevalence of significant mitral regurgitation in group 2. There was no significant difference with respect to age, left atrial size, history of embolism, or warfarin therapy. We conclude that spontaneous echo contrast in the left atrfum of patients with mitral stenosis and normal sinus rhythm is common and is associated with a significantly smaller mitral valve area and higher mitral gmdient. The role of anticoagulation in these patients needs to be prospectively evaluated. (AM HEART J 1994;128:287-92.)

Neil E. Bernstein, MD, Laura A. Demopoulos, MD, Paul A. Tunick, MD, Barry P. Rosenzweig, MD, and Itzhak Kronzon, MD New York, N. Y.

From the Charles tory, Department Received Reprint University

and Rose Wohlstetter Noninvasive of Medicine, New York University

for publication

Nov.

1, 1993;

accepted

requests: Paul A. Tunick, MD, Department Medical Center, 560 First Ave., New

Copyright n 1994 000%8703/94/$3.00

by Mosby-Year + 0 4/l/66666

Book,

Inc.

Cardiology LaboraMedical Center. Dec.

13, 1993.

of Medicine, New York, NY 10016.

York

Dynamic smokelike echoes seen during an ultrasound examination were first reported in 1981.l These swirling echoes, now usually referred to as “spontaneous echo contrast,” were believed to occur in areas of vascular stasis. Spontaneous echo contrast also has been noted in cardiac chambers, and trans287

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Table I. Patients with mitral stenosisand normal sinus rhythm

Mitral valve area(cm2) Meantransmitralgradient(mmHg) Left atria1size(cm) Mitral regurgitation 0 or l+ (n)

Group 1 (SEC) n = 21

Group 2 (no SEC)

1.0 r 0.5 13.6 + 5.2 5.4 t 0.7

1.4 * 0.5 10.5 * 4.9 5.1 zk 0.8


15 6 6

13 13 9 8 54 + 17

NS NS NS

2+ or 3+ fn)

History of embolus(n) Warfarin (n)

8

Age (yr) Mitral regurgitation: NS, Not significant;

47 * 19 0, none; l+, mild; 2+, moderate; echo contrast.

n = 26

P

NS NS

3+, severe.

SEC, spontaneous

esophageal echocardiography is more sensitive for the detection of this phenomenon than transthoracic echocardiography because of the closer proximity of the transducer to the heart and the higher frequencies used. Left atrial spontaneous echo contrast has been noted to occur in conditions favoring stagnation of blood flow. In particular, mitral stenosis has been associated with the presence of spontaneous echo contrast,2-5 which has been reported to be an independent predictor of thromboembolic risk.2 The majority of studies examining the factors responsible for the formation of spontaneous echo contrast in patients with mitral stenosis have focused on patients with the heart in atria1 fibrillation. The purpose of this study was to determine the correlates of spontaneous echo contrast in patients with mitral stenosis and normal sinus rhythm. METHODS We retrospectively reviewed the recordsof 2179patients who had undergone transesophagealechocardiography from January 1, 1989, through April 1, 1993. Before the transesophagealstudy, a standard transthoracic echocardiogram was performed. All transesophagealstudieswere performed after written consent had been obtained. Patients fasted for a minimum of 4 hours, The procedure was performed with patients in the left lateral position after a topical anesthetic spray had been used. No intravenous anesthetic or drying agents were used. Transthoracic studies were performed with Sonos500,1000, or 1500machines (Hewlett-Packard Co., Medical Products Group, Andover, Mass.) with a 2.5 MHz transducer. Transesophageal studies were performed on Sonos 1000 or 1500 (Hewlett-Packard) machineswith monoplane,biplane, or omniplane probes with a 5 MHz transducer. A review of the transesophagealechocardiogramreports identified 67 cases(3%) of mitral stenosis.The transesophageal and transthoracic studies and patient histories stored in a databasewere reviewed. Normal sinus rhythm was present during the echocardiographicexamination in

47 (70%) of 67patients, who madeup the study group. Left atria1 size was measuredin the parasternal long-axis view from the transthoracic study according to the recommendations of the American Society of Echocardiography. Mitral valve area was calculated by the pressurehalf-time method. The mean mitral diastolic gradient was determined by continuous-waveDoppler and calculated with an off-line computer program (Sony, Inc., Tokyo, Japan). Mitral regurgitation was assessed qualitatively by the colorflow regurgitant area and graded asnone, mild, moderate, or severe. Spontaneous echo contrast was defined as dynamic smokelike echoeswith a characteristic swirling motion distinct from white-noise artifact. If spontaneous echocontrast was not seen at normal gain settings, the gain was turned up in the transesophagealstudies to see if spontaneousecho contrast waspresent. Statistical analysis. Data were analyzed by computer (Macintosh IIcx, Apple, Cupertino, Calif.) and StatView statistical software (BrainPower, Inc., Calabasas,Calif.). Nonparametric variables were compared by chi square analysis.Continuous variables were comparedby meansof an unpaired, two-tailed Student’s t test. A p value I 0.05 was consideredstatistically significant. RESULTS

The clinical and echocardiographic features of patients with and without left atrial spontaneous echo contrast are shown in Table I. Of the 47 patients studied, none had undergone mitral valve replacement, and only 1 had undergone mitral valve commissurotomy. Indications for the transesophageal study were evaluation of valve morphologic characteristics in 17 (36%) patients, search for embolic source in 13 (28% ), mitral balloon valvuloplasty in 9 (19%), endocarditisin5 (ll%), andother indications in 3 (6 % ) (evaluation of mitral valve commissurotomy in 1, evaluation for possible intracardiac tumor in 1, and evaluation of the need for anticoagulation in 1). Spontaneous echo contrast was not seen in any of the 47 patients on the transthoracic echocardio-

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Fig. 1. Transesophageal echocardiogram, horizontal plane, demonstrating dramatic swirling echoes in left atrium, representing spontaneous echo contrast. A, aorta; LA, left atrium; LV, left ventricle; RA right atrium.

gram but it was seen in 21 (45%) of the 47 patients on the transesophageal echocardiogram (Fig. 1). One patient with spontaneous echo contrast was found to have a left atria1 thrombus. The patients were divided into two groups. Group 1 consisted of 21 patients with spontaneous echo contrast, and group 2 consisted of 26 patients in whom spontaneous echo contrast was absent. The patients were predominantly women 16 (76 % ) of 21 in group 1 and 20 (77 % ) of 26 in group 2 0, value not significant [NS]). The mean ages of the patients were 47 + 19 and 54 + 17 years (p = NS) in groups 1 and 2, respectively. Six (29%) patients in group 1 had a history of a thromboembolic event before the transesophageal study, compared with 9 (35%) of the group 2 patients (p = NS). In addition, there was no difference between groups in the number of patients taking warfarin (8 [38% ] in group 1 vs 8 [31% ] in group 2). Mitral valve area. In group 1 patients the mean mitral valve area was 1.0 * 0.5 cm2 (range 0.4 to 2.9 cm2). In group 2 patients the mean mitral valve area was 1.4 + 0.5 cm2 (range 0.5 to 2.5 cm2). Mitral valve area was significantly smaller in patients with spontaneous echo contrast (p < 0.02). Mitral valve gradient. The mean transmitral gradient in group 1 patients was 13.6 + 5.2 mm Hg (range 2 to 21 mm Hg). In group 2 patients the mean gradient was 10.5 k 4.9 mm Hg (range 3 to 20 mm Hg). Thus the mean mitral gradient was significantly

higher in patients (p < 0.05).

with spontaneous

echo contrast

Left atrial size. There was no significant difference in left atria1 size between group 1 patients (mean 5.4 +- 0.7 cm, range 4.5 to 6.6 cm) and group 2 patients (mean 5.1 1 0.8 cm, range 3.7 to 7.0 cm) (p NS). Mitral regurgitation. In group 1 there were 2 patients with no mitral regurgitation, 13 with mild regurgitation, 3 with moderate regurgitation, and 3 with severe regurgitation. In group 2 there were 2 patients with no mitral regurgitation, 11 with mild regurgitation, 10 with moderate regurgitation, and 3 with severe regurgitation. There was no statistically significant difference between the groups. When the data were analyzed on the basis of the absence of or the presence of mild regurgitation versus moderate or severe regurgitation, there was a trend toward a lower prevalence of moderate or severe regurgitation in the patients with spontaneous echo contrast, although this trend did not reach statistical significance. In group 1, only 6 (29 %) of 21 patients had moderate or severe regurgitation compared with 13 (50% ) of 26 patients in group 2 (p 0.13). DISCUSSION

Swirling smokelike echoes, commonly called spontaneous echo contrast, are an occasional finding during echocardiography. These echoes are associated with conditions favoring stasis of flow. Although the

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exact mechanism of their appearance is unknown, red blood cell aggregation is believed to play a role. Red blood cells, because of their small size, usually are invisible to the frequencies of sound waves used during echocardiography. During low-flow states, red blood cells may aggregate (Rouleaux formation). Because of their larger size, these aggregates may be visible on echocardiograms, particularly with transesophageal echocardiography. Because higher-frequency transducers are used, resolving power is increased. The role of platelets in the formation of spontaneous echo contrast is still unclear.7p 8 In vitro experiments on blood echogenicity show that the formation of spontaneous echo contrast does not appear to be influenced by heparin,l and although anticoagulation reduces the number of embolic events, clinical studies have failed to detect any affect of chronic anticoagulation on the presence of spontaneous echo contrast.2p g Spontaneous echo contrast has been identified in many different pathologic conditions. It has been seen in the left ventricle in patients with dilated cardiomyopathieslO and the false lumen of an aortic dissection.ll The spontaneous echo contrast seen in the left atrium associated with conditions such as atria1 fibrillation and mitral stenosis, however, is probably the best studied. The majority of studies examining spontaneous echo contrast in mitral stenosis have focused on patients with the heart in atria1 fibrillation. Black et a1.g prospectively studied 400 consecutive cases of patients who underwent transesophageal echocardiography and identified 75 with spontaneous echo contrast. Of these 400, only 49 had mitral stenosis, and in 21 (43 % ) of these the heart was in normal sinus rhythm. Spontaneous echo contrast was visualized in 6 (29 % ) of 21 patients with normal sinus rhythm and mitral stenosis, and none was seen in the remaining 15 (71%). Daniel et a1.2 studied 52 patients with mitral stenosis with transesophageal echocardiography and found spontaneous echo contrast in 3.5 (67 % ). Of these 52 patients, the hearts of 16 were in normal sinus rhythm (31%). Only 6 (38%) of these 16 were found to have spontaneous echo contrast. Beppu et a1.3 studied 116 consecutive patients with rheumatic mitral valve disease by using transthoracic echocardiography with a 2.4 MHz transducer and found that 37 (32%) of 116 had spontaneous echo contrast. In only 17 patients (15 % ) was the heart in normal sinus rhythm, and none was noted to have detectable spontaneous echo contrast. Only a study by Cormier et a1.5 included a large number of patients with mitral stenosis and normal sinus rhythm. These investigators performed transesophageal echocardiogra-

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phy on 82 patients before and after percutaneous mitral balloon valvuloplasty. Of these 82, the hearts of 59 (72 % ) were in sinus rhythm, and 30 (51% ) of 59 were noted to have spontaneous echo contrast prior to commissurotomy. Our current study included 47 patients with mitral stenosis and normal sinus rhythm. We found 45% to have spontaneous echo contrast. This frequency of spontaneous echo contrast approximates that found in the study by Cormier et al.: which focused on changes after valvuloplasty. Transesophageal echocardiography appears to be far more sensitive than standard transthoracic echocardiography for the detection of spontaneous echo contrast. Only the study by Beppu et a1.3relied solely on transthoracic echocardiography to study the features and clinical significance of spontaneous echo contrast. Black et a1.g did not visualize spontaneous echo contrast with transthoracic echocardiography in any of their 400 patients, and Daniel et a1.2 identified only 1 case (0.8%) of spontaneous echo contrast of 122 studied. Similarly, we found transthoracic echocardiography to be insensitive for visualizing spontaneous echo contrast. Although 21 of the 47 patients we studied were noted to have spontaneous echo contrast by transesophageal echocardiography, none was identified by transthoracic imaging. Mitral valve area. The mean mitral valve area in our patients with spontaneous echo contrast was significantly smaller than that found in those without spontaneous echo contrast. This difference is in accordance with data from several previous reports. Black et a1.g found the mean mitral valve area to be 1.1 f 0.3 cm2 compared with 1.4 f 0.3 cm2 in patients with no spontaneous echo contrast. Similarly, the Beppu et al3 found the mitral valve area to be 0.7 + 0.2 cm2 in patients with severe contrast, 1.1 + 0.4 cm2 in patients with mild contrast, and 1.5 +- 0.8 cm2 in patients without spontaneous echo contrast. In the Daniel et al2 study, in which measurements were obtained at cardiac catheterization, there was no difference in mean valve area between those with and those without spontaneous echo contrast, but this result might be explained by the small valve area in both groups (mean < 1.0 cm2 in both) and the small number of patients studied (valve area calculated for only 21 of the 52 patients with mitral stenosis). Mitral valve gradient. The mean transmitral gradient was significantly greater in our patients with spontaneous echo contrast than in those without spontaneous echo contrast. This finding is in contrast to several previous studies that failed to show a significant difference in the transvalvular gradient. Black et a1.gfound the mean gradients to be 8.7 +- 4.7

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and 8.9 +- 4.7 mm Hg in patients with contrast versus those without contrast, respectively (p NS), and Daniel et a1.2 found the gradients to be 14.8 + 5.8 and 15.3 ? 6.3 mm Hg (contrast vs no contrast, respectively; p NS). However, in the Black et al9 study, of the 27 patients with mitral stenosis and spontaneous echo contrast, the hearts of only 6 were in sinus rhythm. Similarly, in the Daniel et al2 study, which included 52 patients with mitral stenosis, the hearts of only 6 patients with spontaneous echo contrast (of 35) were in sinus rhythm. The finding of a statistically significant higher gradient in patients with spontaneous echo contrast and sinus rhythm is in accordance with the current theories on the pathogenesis of spontaneous echo contrast. Because contrast is the result of stasis of flow, a reduced mitral valve area would be expected to contribute to a higher mean transmitral gradient and to blood stasis. Left atrial size. Left atria1 size was slightly larger in patients with spontaneous echo contrast than in those without spontaneous echo contrast, but the difference was not statistically significant. Several groups2-4 have found left atria1 size to be significantly greater in patients with spontaneous echo contrast than in those without it, but those studies focused primarily on patients with atria1 fibrillation. Cormier et a1.5 also found left atria1 size to be an independent predictor of spontaneous echo contrast. Although their study included 59 (72 % ) patients with sinus rhythm, the data for left atrial size were evaluated without distinguishing patients with atria1 fibrillation from those with sinus rhythm. In patients with mitral stenosis and normal sinus rhythm, it is possible that left atria1 size may not play as significant a role as mitral valve area and mitral valve gradient in the development of spontaneous echo contrast because the effect of atria1 size may be overshadowed by the role of the effectiveness of atria1 contraction. Mitral regurgitation. Although we found no statistically significant relation between the degree of mitral regurgitation and spontaneous echo contrast, there was a trend toward an association between moderate or severe regurgitation and the absence of spontaneous echo contrast. Only Caste110 et a1.4 have found a positive relation between the presence of mitral regurgitation and spontaneous echo contrast. In a study of 150 consecutive patients undergoing transesophageal echocardiography, they identified 25 with left atria1 spontaneous echo contrast. Twelve (48%) of these 25 patients had moderate or severe mitral regurgitation compared with 31 (26%) of 121 patients without spontaneous echo contrast (p = 0.03). Their study, however, included only a very small

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number of patients with mitral stenosis (only 12 of 146 patients) and a large number of patients with prosthetic mitral valves, primary mitral regurgitation, and left ventricular dysfunction. Other studies3Tg have suggested that mitral regurgitation is protective against spontaneous echo contrast formation. Movsowitz et a1.12retrospectively examined the relation between mitral regurgitation and spontaneous echo contrast in 427 consecutive patients undergoing transesophageal echocardiography. They found that 9 % of patients with no, mild, or moderate mitral regurgitation had spontaneous echo contrast compared with < 1% of patients with moderate to severe or severe mitral regurgitation (p < 0.03). Cormier et a1.5 found that the only predictor of the disappearance of spontaneous echo contrast in patients with mitral stenosis and atria1 fibrillation after percutaneous mitral balloon valvuloplasty was the presence of severe mitral regurgitation. Because the cause of spontaneous echo contrast is believed to be stasis of flow, it is not unexpected that left atrial “washout” from significant mitral regurgitation may reduce the incidence of spontaneous echo contrast in patients with mitral valve disease. Other determinants

of spontaneous

echo contrast.

We did not evaluate other mechanisms for the production of spontaneous echo contrast, such as hematologic or rheologic factors. Low shear rates have been associated with spontaneous contrast formation.3 Other investigators l3 have found factors such as hematocrit and fibrinogen levels to be important. Jolly et al., I4 studying the relation between spontaneous echo contrast and pulmonary venous flow patterns in patients with mitral stenosis and normal sinus rhythm, found no significant differences in the pulmonary venous flow patterns when comparing patients with and without spontaneous echo contrast. They concluded that the occurrence of spontaneous echo contrast in patients with mitral stenosis was not related to pulmonary venous flow and that other factors besides the severity of the mitral stenosis may be involved. Limitations. A major limitation of this study is its retrospective design. Because patients are often referred for transesophageal echocardiography because of embolic events or other episodes of clinical deterioration, a significant referral bias exists. This bias may account in part for the lack of a significant difference between patients with and without spontaneous echo contrast in the incidence of previous embolic events. In addition, there may have been many patients with mitral stenosis who had embolic events but who were not referred for transesophageal echocardiography because the event alone was considered

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to be an adequate indication for anticoagulation without further evaluation. Finally, day-to-day variability in cardiac output or other factors may affect the degree of stasis present in the left atrium and may in turn affect the likelihood of finding spontaneous echo contrast on any given transesophageal echocardiographic examination. Conclusions and clinical implications. We have shown that the presence of spontaneous echo contrast in patients with mitral stenosis and normal sinus rhythm is significantly dependent on the severity of the stenosis as reflected by smaller valve areas and higher mean transmitral gradients. The overall prevalence of spontaneous echo contrast in an unselected population of patients with mitral stenosis and sinus rhythm has not been systematically studied, nor has anyone investigated the potential implications for thrombus development and the risk of thromboembolism in this patient population. The requirement for anticoagulation in patients with mitral stenosis and atria1 fibrillation is well known. A major question remains, however, for patients with mitral stenosis and normal sinus rhythm: should anticoagulation be used if spontaneous echo contrast is found on transesophageal echocardiography? A prospective study should be done to compare the clinical outcomes of patients with mitral stenosis and normal sinus rhythm, with and without chronic warfarin therapy.

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Beppu S, Nimura Y, Sakakibara H, Nagata S, Park Y, Izumi S. Smoke-like echo in the left atrial cavity in mitral valve disease: its features and significance. J Am Co11 Cardiol 1985; 6:744-9. Caste110 R, Pearson AC, Labovitz AJ. Prevalence and clinical implications of atria1 spontaneous contrast in patients undergoing transesophageal echocardiography. Am J Cardiol 1990;65:1149-53. Cormier B, Vahanian A, Iung B, Porte JM, Dadez E, Lazarus A, Starkman C, Acar J. Influence of percutaneous mitral commissurotomy on left atria1 spontaneous contrast of mitral stenosis. Am J Cardiol 1993;71:842-7. Wang X, Liu L, Cheng TO, Li Z, Deng Y, Wang J. The relationship between intracardiovascular smoke-like echo and erythrocyte rouleaux formation. AM HEART J 1992;124:961-5. Erbel R. Stern H. Ehrenthal W. Schreiner G. Treese N. Kramer G, Thelen M, Schweizer ‘P, Meyer J. Detection of spontaneous echocardiographic contrast within the left atrium by transesophagesl echocardiography: spontaneous echocardioarauhic contrast. Clin Cardiol 1986:9:245-52. Sio&zonek P, Koppensteiner R, G&singer H, Zangeneh M, Heinz G, Kreiner G, Sttimpflen A, Buxbaum P, Ehringer H, Mosslacher H. Hemodynamic and hemorrheologic determinants of left atrial spontaneous echo contrast and thrombus formation in patients with idiopathic dilated cardiomyopathy. AM HEART

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