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Ann Thorac Surg 1996;62:1790-1795
© 1996 The Society of Thoracic Surgeons

Original Articles: Cardiovascular

Left Atrial Spontaneous Echo Contrast in Asymptomatic Patients With a Mechanical Valve Prosthesis

Tsung-Ming Lee, MD, Nai-Kuan Chou, MD, Sheng-Fang Su, PhD, Yueh-Juh Lin, MD, Ming-Fong Chen, MD, Chiau-Suong Liau, MD, Yuan-Teh Lee, MD, Shu-Hsun Chu, MD

Departments of Internal Medicine and Surgery, Cardiology Section, Center for Cardiovascular Research, College of Medicine, National Taiwan University, National Taiwan University Hospital, Taipei, and College of Medicine, National Cheng Kung University, Tainan, Taiwan

Accepted for publication June 26, 1996.


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
Background. Valve thromboembolism may be a fatal complication of mechanical valve prosthesis if detected late. Spontaneous echo contrast (SEC) is a well-documented prothrombotic phenomenon; here we report it in asymptomatic patients with a mechanical valve prosthesis.

Methods. Ninety-two asymptomatic patients with a mechanical valve prosthesis for underlying rheumatic heart disease underwent transesophageal echocardiography. Appendage area, peak filling and emptying velocities of the left atrial appendage, and the presence or absence of SEC and thrombi were determined. The results of 56 patients without SEC or thrombi (group I) were compared with those of 24 patients with SEC and no thrombi (group II) and 12 patients with thrombi (group III).

Results. Spontaneous echo contrast was present in 39% of the asymptomatic patients with a mechanical valve prosthesis. Although 12 patients had cardiac thrombi, including valve thrombi in 4, no patients presented symptoms. Anticoagulant therapy had no significant association with SEC and atrial thrombi. There was a significantly greater prevalence of atrial fibrillation and mitral prosthesis in groups II and III than in group I. Two patterns of left atrial appendage flow were identified: one was organized biphasic flow with peak filling velocities of 41.2 ± 17.2 cm/s and emptying velocities of 40.5 ± 17.5 cm/s. The other showed irregular, very low peak filling velocities (10.4 ± 11.5 cm/s) and emptying velocities (12.3 ± 13.1 cm/s). The former flow pattern was associated with sinus rhythm and the latter form was associated with atrial fibrillation.

Conclusions. There was a relatively high prevalence of SEC and thrombi in patients with a mechanical valve prosthesis. Patients with a valve prosthesis may not have clinical symptoms. Anticoagulation intensity was not associated with the occurrence of SEC and thrombi. Patients with a mitral valve prosthesis and atrial fibrillation were identified as a high-risk of subgroup for the development of SEC and thrombi.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
See also page 1795.

Mechanical valve obstruction, mostly due to thrombosis, is one of the most serious complications of a mechanical prosthetic valve, with prevalence rates ranging from 0.5% to 6% per patient-year in the aortic and mitral positions [1–3]. Its clinical presentation may vary from no symptoms to abrupt circulatory collapse. Failure to make the diagnosis early and intervene promptly increases the mortality rate.

In the care of patients with mechanical prosthetic valve it would be very helpful if risk factors for thrombus formation could be identified. Spontaneous echo contrast (SEC) is an indicator for an increased thromboembolic risk [4]. Left atrial SEC can be detected by transesophageal echocardiography due to the unique acoustic window from the esophagus to the posterior left atrial wall. Transesophageal echocardiography has also been proved to be a useful tool for the detection of prosthetic valve malfunction. Previous studies focused on the detection of obstructed valves in patients with symptoms related to malfunction of prosthetic valves. Rare data [5] available showed left atrial SEC in patients with normally functioning mechanical valve prosthesis valve.

The present study was conducted in asymptomatic patients with rheumatic heart disease who had a mechanical valve prosthesis. The purpose of this study was (1) to assess the prevalence of left atrial SEC, (2) to investigate the correlation between the presence of left atrial SEC and anticoagulation therapy, (3) and to identify risk factors for left atrial SEC in this specific group of patients with the use of transesophageal echocardiography.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
Patients
During a 6-month period, a total of 92 patients (45 men, 47 women) with rheumatic heart disease who had mechanical prosthetic valves were consecutively studied. Rheumatic heart disease was confirmed by pathologic examination. Patients with left atrial appendage obliteration were excluded. Patients had neither clinical symptoms indicating valvular dysfunction nor echocardiographic prosthetic valvular dysfunction. Thirty-five patients had mitral prosthetic valves, 46 had aortic valves, and 11 had both mitral and aortic valve replacement. The ages ranged from 25 to 78 years, with a mean of 51.4 ± 12.5 years. All patients were receiving oral anticoagulant therapy. The prothrombin time was checked at the time of transesophageal echocardiographic study and reported as a ratio of the control data. The same dose of anticoagulant was maintained for at least 7 days before the prothrombin time was checked. Antiplatelet agents and dipyridamole were not used in any patient. After transesophageal echocardiographic study, the patients were separated into three groups according to the presence or absence of left atrial SEC and thrombus. Group I consisted of 56 patients with no SEC or thrombus; group II, 24 patients with SEC but no thrombus; and group III, 12 patients with thrombus in the left atrium or appendage. Clinical data of the patients are summarized in Table 1Go. The mean implantation time was 68.3 ± 37.5 months for group I patients, 80.5 ± 28.6 months for group II patients, and 65.6 ± 29.5 months for group III patients.


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  		Table 1. . Clinical Characteristics in Different Patient Groupsa
 
Echocardiography
Transthoracic and transesophageal echocardiographic studies were performed on the same day in all patients. Echocardiographic examination was performed with the use of a Hewlett-Packard Sonos 2500 equipped with a 2.5-MHz transducer. M-mode measurements were obtained according to the criteria of the American Society of Echocardiography [6] to detect left atrial, left ventricular end-systolic, and left ventricular end-diastolic dimensions, and left ventricular fractional shortening. For transesophageal echocardiography, a 5-MHz biplane or multiplane transducer was used. Patients had fasted for 6 hours before transesophageal echocardiography. Local pharyngeal anesthesia with 8% lidocaine spray was the only premedication. During echocardiography, a one-lead electrocardiogram was recorded. Informed consent was obtained from all patients and normal control subjects. The study was approved by the institutional research ethics committee.

LEFT ATRIAL APPENDAGE AREA AND FLOW.
Images of the left atrial appendage were obtained in the transverse and longitudinal planes and recorded on Super VHS videotapes for off-line analysis. The boundary of the base of the appendage was defined by a line drawn from the limbus of the left upper pulmonary vein to the most exterior portion of the mitral annulus. Maximal and minimal left atrial appendage areas were determined by computed planimetry along the endocardial border of the left atrial appendage (average of three consecutive values). The ejection fraction of the left atrial appendage was calculated as (maximal area - minimal area)/maximal area. Left atrial appendage velocity profiles were obtained by pulsed wave Doppler interrogation at the orifice of the appendage. The maximal forward positive flow velocity of Doppler left atrial appendage represented the peak emptying velocity and the maximal backward negative flow velocity of Doppler left atrial appendage represented the peak filling velocity. Peak emptying and filing velocities were averaged with each RR interval over a minimum of five cardiac cycles for patients with atrial fibrillation, and over three cardiac cycles in case of sinus rhythm. Interobserver differences were resolved by consensus.

SPONTANEOUS ECHO CONTRAST AND THROMBUS.
Left atrial SEC was identified by the presence of dynamic smoke-like echoes within the atrial cavity, with a characteristic swirling motion distinct from white noise artifact [7]. The gain was continuously adjusted to ensure the best possible visualization and to avoid noise artifact. Left atrial "microbubbles" were occasionally observed with the characteristics of bright echogenicity, which were differentiated from typical left atrial SEC [5]. Thrombi were defined as masses adherent to the wall of the left atrial appendage with different echogenic density. Particular attention was paid to differentiate thrombi from pectinate muscles. The consensus of two experienced echocardiographers defined the presence or absence of SEC and thrombi.

Statistics
Values are reported as mean value ± 1 standard deviation. A {chi}2 test was used to compare categoric variables. For comparison of multiple groups, analysis of variance was used. The correlation between the intensity of anticoagulation and the presence of atrial SEC and thrombi was compared by both continuous and categoric analysis. A p value less than 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Figures 1 and 2GoGo show typical Doppler flow patterns of the left atrial appendage in sinus rhythm and atrial fibrillation, respectively. Figures 3, 4, and 5GoGoGo show typical thrombi on mitral prosthetic valve and left atrial wall and in left atrial appendage, respectively. Left atrial SEC was detected in 39% of the patients, whereas left atrial thrombi were detected in 13% of the patients.



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  		Fig 1. . Left atrial appendage flow patterns of longitudinal transesophageal echocardiography in patients with sinus rhythm. There are well-defined biphasic filling and emptying waves. The maximal forward positive flow velocity (a wave) is the peak emptying velocity; the maximal backward negative flow velocity (b wave) is the peak filling velocity.

 


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  		Fig 2. . Left atrial appendage flow patterns of longitudinal transesophageal echocardiography in patients with atrial fibrillation. There are irregular, low emptying and filling waves.

 


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  		Fig 3. . Longitudinal transesophageal echocardiography in a woman with a Medtronic-Hall mechanical valve prosthesis. A nonobstructed valve thrombus (arrows) at the mechanical mitral valve resolved after treatment with plasminogen activator. There was also an obvious spontaneous echo contrast phenomenon at the left atrium. The prothrombin time at the time of transesophageal echocardiographic examination was 1.9 times control value.

 


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  		Fig 4. . A huge thrombus (arrowheads) at the posterior wall of the left atrium in a 43-year-old man with a CarboMedics mitral valve prosthesis was detected during routine transesophageal echocardiography in this study. There was also an obvious spontaneous echo contrast phenomenon at the left atrium. The prothrombin time at the time of transesophageal echocardiographic examination was 1.7 times control value.

 


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  		Fig 5. . A small thrombus (arrow) was demonstrated at the left atrial appendage in a woman with a St. Jude aortic valve. There was also an obvious spontaneous echo contrast phenomenon at the left atrium. The prothrombin time at the time of transesophageal echocardiographic examination was 1.5 times control value.

 
Clinical Variables
The clinical characteristics of the patients are presented in Table 1Go. Left atrial SEC was present in all patients of group III. In group III, 4 patients with valve thrombi (see Fig 3Go) received thrombolysis with tissue plasminogen activator, and repeated TEE examination revealed no more thrombi in each patient. Two patients had thrombi in the left atrium and 6 in the left atrial appendage.

There was a significantly greater presence of atrial fibrillation and mitral prosthesis in groups II and III than in group I (p < 0.01 and <0.001, respectively). The level of anticoagulation at the time of study was therapeutic (prothrombin time at least 1.5 times control values) in 72% of group I, 67% of group II, and 50% of group III (p = not significant). The intensity of anticoagulation was not significant among the three groups by both continuous and categoric analysis. Valve type and the mean time elapsed from valve replacement to the study were not significantly different among the three groups.

Echocardiographic Measurements
The echocardiographic measurements are presented in Table 2Go. The left atrial size was significantly larger in groups II and III than in group I. The fractional shortening of the left ventricle was significantly less in group III than in groups I and II.


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  		Table 2. . Echocardiographic Measurementsa
 
Two patterns of left atrial appendage flow were identified. In patients with sinus rhythm, Doppler image revealed a biphasic flow pattern with a peak filling velocity of 10 to 70 cm/s (mean, 41.2 ± 17.2 cm/s) and an emptying velocity of 15 to 62 cm/s (mean, 40.5 ± 17.5 cm/s). The Doppler a wave occurred after the electrocardiographic P wave and the Doppler b wave followed the Doppler a wave. In patients with atrial fibrillation, the left atrial appendage flow showed irregular, very low peak filling (range, 4 to 39 cm/s; mean, 10.4 ± 11.5 cm/s) and emptying (5 to 43 cm/s; mean, 12.3 ± 13.1 cm/s) velocities. The left atrial appendage peak filling and emptying velocities of patients with atrial fibrillation were significantly less than those of patients with sinus rhythm (both p < 0.0001). The odds ratio for spontaneous echo contrast was 6.2:1 for low left atrial appendage velocity (<35 cm/s). The maximal and minimal areas of the left atrial appendage were significantly greater in patients with atrial fibrillation than in patients with sinus rhythm. The ejection fraction of the left atrial appendage was significantly less in atrial fibrillation than in sinus rhythm. There were almost no visible appendage contractions in atrial fibrillation.

Ejection fractions of the left atrial appendage were significantly less in groups II and III than in group I. The peak filling and emptying velocities of the left atrial appendage were greater in group I than in groups II and III.


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
In this study, we have demonstrated left atrial SEC and thrombi in a group of asymptomatic rheumatic heart disease patients with a mechanical valve prosthesis. Left atrial SEC or thrombus was detected in 39% of our patients. Patients with valve thrombi may be symptom-free and respond well to thrombolysis treatment. Patients with a mitral valve prosthesis and atrial fibrillation were found at an increased risk of left atrial SEC and thrombi. There was no correlation between the occurrence of left atrial SEC and thrombi and the level of anticoagulation.

Left Atrial Spontaneous Echo Contrast
Left atrial SEC is a phenomenon than usually appears at regions of blood stasis including enlarged left atrium and areas of the left ventricle with impaired function, as was seen in this study; however, the mechanism of this phenomenon remains unclear. The pathogenesis of SEC is complex and includes not only the velocity or shear rate of local blood flow but also factors such as abnormalities of blood components. Siegel and associates [8] suggested that rouleaux formation of erythrocytes and increased level of serum fibrinogen may be responsible for its production. However, Erbel and colleagues [9] showed evidence of increased platelet aggregation in all their patients. Mahony and associates [10] reported a patient with left ventricular SEC despite heparin treatment in whom platelet aggregates were detected in the peripheral blood. Complete SEC resolution was noted after 5 days of antiplatelet treatment. Thus further studies are warranted comparing the therapeutic value of anticoagulant and antiplatelet drugs in patients with SEC.

The relationship between SEC and thrombus formation has been previously studied. Our results indicated that SEC was present in all patients with atrial thrombi, which agreed with the findings of a previous study [11]. Patients with left atrial SEC were 27 times more likely to have had a previous stroke or peripheral embolism than patients without SEC [11]. Daniel and associates [4] demonstrated that in patients with mitral valve disease, left atrial SEC was an independent predictor of left atrial thrombus and cardiogenic embolism.

Clinical Predictors of Spontaneous Echo Contrast
Our results suggest than atrial fibrillation and mitral valve prosthesis were the major clinical conditions favoring the development of SEC. In atrial fibrillation, the absence of organized atrial contraction results in a disorganized flow pattern and reduced velocities of emptying and filling flows. Mugge and colleagues [12] meticulously divided patients with atrial fibrillation into two subgroups on the basis of left atrial appendage function. One group had a high flow profile with high peak filling and emptying velocities of the left atrial appendage; the other had a low flow profile with very low peak filling and emptying velocities. Their results showed that the prevalence of SEC was significantly greater in patients in the low-flow profile subgroup than in patients with the high flow profile. In patients with rheumatic heart disease, like our study subjects, the left atrial appendage may be susceptible to rheumatic inflammation [13], resulting in impaired left atrial appendage function. Thus, rheumatic patients with atrial fibrillation flow patterns of the left atrial appendage were expected to have low flow profiles and a high prevalence of SEC.

Mitral valve prosthesis was also found to be significantly related to the occurrence of left atrial SEC. Toy and colleagues [14] demonstrated that platelet aggregation was significantly greater in patients with rheumatic mitral valve disease than in patients with rheumatic aortic valve disease. Kelley and colleagues [13] showed that in patients with rheumatic heart disease the size of the left atrial appendage was greater if the mitral valve was involved. In addition, there was an increased prevalence of atrial fibrillation in rheumatic mitral valve disease than in rheumatic aortic valve disease. Conditions favoring blood stasis in the left atrium included left atrial and appendage dilation and atrial fibrillation, which have also been demonstrated to be associated with the development of left atrial SEC.

Our results do not show differences in the production of left atrial SEC by different types of prosthetic valves. Previous studies [15] showed that there are some differences in the prevalence of thromboembolism among different mechanical valves. In our study with a relatively small population, type II error should be considered.

Anticoagulation
Our results showed that the level of anticoagulation did not correlate with the occurrence of left atrial thrombi by continuous and categoric analysis. Previous studies [16–18] emphasized the importance of well-controlled anticoagulation in the prevention and treatment of cardiac thrombi in mechanical valve prostheses. This discrepancy may be explained as follows: First, our group III patients are symptom-free but have thrombi in the left atrium, which is different from the symptomatic patients of previous reports. Second, in this study, patients consisted of a homogeneous group with rheumatic heart disease. Patients with rheumatic heart disease had an increased coagulable tendency in blood [14]. The generally recommended international normalized ratio varies widely from 1.9 to 4.8 [17, 19] for preventing thromboembolism in patients with a mechanical valve prosthesis. There is no report on the optimal anticoagulation for rheumatic patients with valve prostheses. Finally, type II error cannot be definitely ruled out because of the relatively small number of patients studied.

Conclusions
Left atrial SEC was a common finding in asymptomatic rheumatic patients with a mechanical valve prosthesis. Left atrial SEC was associated with conditions favoring blood stasis, including atrial fibrillation, mitral valve prosthesis, left atrial enlargement, and depressed function of the left ventricle. Anticoagulation intensity had no association with SEC and atrial thrombosis.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. Lee TM, Chu SH, Wang LC, Lee YT. Thrombolysis for obstructed CarboMedics mitral valve prosthesis. Ann Thorac Surg 1995;59:509–11.[Abstract/Free Full Text]
  2. Edmunds LH. Thromboembolic complications of current cardiac valvular prosthesis. Ann Thorac Surg 1982;34:96–104.[Abstract/Free Full Text]
  3. Martinell J, Frail J, Artiz V, Cortina J, Fransneda P, Rabago G. Reoperation for left sided low profile mechanical prosthetic obstruction. Ann Thorac Surg 1987;43:172–5.[Abstract/Free Full Text]
  4. Daniel WG, Nellesen U, Schroder E, et al. Left atrial spontaneous echo contrast in mitral valve disease: an indicator for an increased thromboembolic risk. J Am Coll Cardiol 1988;11:1204–11.[Abstract]
  5. Reisner SA, Rinkevich D, Markiewicz W, Adler Z, Milo S. Spontaneous echocardiographic contrast with the Carbomedics mitral valve prosthesis. Am J Cardiol 1992;70:1497–500.[Medline]
  6. Sahn PS, De Maria A, Kisslo J, Weyman A. The committee of the M-mode standardization of the American Society of Echocardiography. Recommendations regarding quantification on the M-mode echocardiography: results of survey of echocardiographic measurements. Circulation 1978;58:1072–81.[Abstract/Free Full Text]
  7. Castello R, Pearson AC, Labovitz AJ. Prevalence and clinical implications of atrial spontaneous contrast in patients undergoing transesophageal echocardiography. Am J Cardiol 1990;65:1149–53.[Medline]
  8. Siegel B, Coelho JO, Spigos DG, et al. Ultrasonography of blood during stasis and coagulation. Invest Radiol 1981;16:71–6.[Medline]
  9. Erbel R, Stern H, Ehrenthal W, et al. Detection of spontaneous echocardiographic contrast within the left atrium by transesophageal cardiography: spontaneous echocardiographic contrast. Clin Cardiol 1986;9:245–52.[Medline]
  10. Mahony C, Sublett KL, Harrison MR. Resolution of spontaneous contrast with platelet disaggregatory therapy (Trifloperazine). Am J Cardiol 1989;63:1009–10.[Medline]
  11. Chimowitz MI, DeGeorgia MA, Poole RM, Hepner A, Armstrong WM. Left atrial spontaneous echo contrast is highly associated with previous stroke in patients with atrial fibrillation or mitral stenosis. Stroke 1993;24:1015–9.[Abstract/Free Full Text]
  12. Mugge A, Kuhn H, Nikutta P, Grote J, Lopez AG, Daniel WG. Assessment of left atrial appendage function by biplane transesophageal echocardiography in patients with nonrheumatic atrial fibrillation: identification of a subgroup of patients at increased embolic risk. J Am Coll Cardiol 1994;23:599–607.[Abstract]
  13. Kelley MJ, Elliott LP, Shulman ST, Ayoub EM, Victorica BE, Gessner IH. The significance of the left atrial appendage in rheumatic heart disease. Radiology 1976;54:146–53.
  14. Toy JL, Lederer DA, Tulpule AT, Tandon AP, Taylor SH, McNicol GP. Coagulation studies in rheumatic heart disease. Br Heart J 1980;43:301–5.[Abstract/Free Full Text]
  15. Akins CW. Results with mechanical cardiac valvular prostheses. Ann Thorac Surg 1995;60:1836–44.[Abstract/Free Full Text]
  16. Altman R, Rouvier J, Gurfinkel E, et al. Comparison of two levels of anticoagulant therapy in patients with substitute heart valves. J Thorac Cardiovasc Surg 1991;101:427–31.[Abstract]
  17. Horstkotte D, Schulte HD, Bircks W, Strauer BE. Lower intensity anticoagulant therapy results in lower complication rates with St. Jude Medical prosthesis. J Thorac Cardiovasc Surg 1994;107:1136–45.[Abstract/Free Full Text]
  18. Butchart EG, Lewis PA, Grunkemeier GL, Kulatilake N, Breckenridge IM. Low risk of thrombosis and serious embolic events despite low-intensity anticoagulation: experience with 1,004 Medtronic Hall valves. Circulation 1988;78(Suppl 1):I66–77.[Medline]
  19. Loeliger EA. Therapeutic target values in oral anticoagulation-justification of Dutch policy and a warning against the so-called moderate-intensity regimens. Ann Haematol 1992;64:60–5.[Medline]

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