Ian W. Black

Left atrial spontaneous echo contrast: A clinical and echocardiographic analysis

The clinical and echocardiographic variables related to left atrial spontaneous echo contrast were prospectively evaluated in a consecutive series of 400 patients undergoing transesophageal echocardiography with a 5-MHz single plane transducer. Left atrial spontaneous echo contrast was found in 75 patients (19%) and was significantly associated with atrial fibrillation, mitral stenosis, absence of mitral regurgitation, increased left atrial dimension and a history of suspected embolism. Seventy-one (95%) of the patients with spontaneous echo contrast had atrial fibrillation or mitral stenosis. Anticoagulant therapy had no significant association with spontaneous echo contrast. Multivariate analysis in 89 patients with mitral stenosis or mitral valve replacement showed that spontaneous echo contrast was the only independent predictor (p = 0.03) of left atrial thrombus or suspected embolism, or both. In 60 patients with atrial fibrillation of nonvalvular origin, spontaneous echo contrast (p = 0.01) and age (p = 0.03) were the only independent predictors of left atrial thrombus or suspected embolism, or both. It is concluded that left atrial spontaneous echo contrast is 1) a common finding in patients undergoing transesophageal echocardiography, 2) associated with conditions favoring stasis of left atrial blood, and 3) a marker of previous thromboembolism in patients with nonvalvular atrial fibrillation and those with mitral stenosis or mitral valve replacement.

Prognostic implications of left artial spontaneous echo contrast in nonvalvular atrial fibrillation

OBJECTIVES This study examined the influence of left atrial spontaneous echo contrast on the subsequent stroke or embolic event rate and on survival in patients with nonvalvular atrial fibrillation. BACKGROUND Left atrial spontaneous echo contrast is associated with atrial fibrillation and a history of previous stroke or other embolic events. However, the prognostic implications of spontaneous contrast in patients with nonvalvular atrial fibrillation are unknown. METHOD The study group comprised 272 consecutive patients with nonvalvular atrial fibrillation undergoing transesophageal echocardiography. Clinical and echocardiographic data were collected at baseline, and patients were prospectively followed up, and all strokes, other embolic events and deaths were documented. The relation between spontaneous contrast at baseline and subsequent stroke, other embolic events and survival was analyzed. RESULTS Left atrial spontaneous echo contrast was detected at baseline in 161 patients (59%). The mean follow-up was 17.5 months. The stroke or other embolic event rate was 12%/year (15 strokes, 3 transient ischemic attacks, 2 peripheral embolisms) in patients with, compared with 3%/year (5 strokes) in patients without, baseline spontaneous contrast (p = 0.002). In 149 patients without previous thromboembolism, the event rate was 9.5%/year in patients with and 2.2%/year in patients without spontaneous contrast (p = 0.003). There were 25 deaths in patients with and 11 deaths in patients without spontaneous contrast. Patients with spontaneous contrast had significantly reduced survival (p = 0.025). On multivariate analysis, spontaneous contrast was the only positive predictor (odds ratio 3.5, p = 0.03) and warfarin therapy on follow-up the only negative predictor (odds ratio 0.23, p = 0.02) of subsequent stroke or other embolic events. CONCLUSIONS Transesophageal echocardiography can risk stratify patients with nonvalvular atrial fibrillation by identifying left atrial spontaneous echo contrast. These patients have both a significantly higher risk of developing stroke or other embolic events and a reduced survival, and they may represent a subgroup in whom the risk/benefit ratio of anticoagulation may be most favorable.

Exclusion of atrial thrombus by transesophageal echocardiography does not preclude embolism after cardioversion of atrial fibrillation. A multicenter study.

BACKGROUND Transesophageal echocardiography (TEE) has been used recently to detect atrial thrombi before cardioversion of atrial arrhythmias. It has been assumed that embolic events after cardioversion result from embolism of preexisting atrial thrombi that are accurately detected by TEE. This study examined the clinical and echocardiographic findings in patients with embolism after cardioversion of atrial fibrillation despite exclusion of atrial thrombi by TEE. METHODS AND RESULTS Clinical and echocardiographic data in 17 patients with embolic events after TEE-guided electrical (n = 16) or pharmacological (n = 1) cardioversion were analyzed. All 17 patients had nonvalvular atrial fibrillation, including four patients with lone atrial fibrillation. TEE before cardioversion showed left atrial spontaneous echo contrast in five patients and did not show atrial thrombus in any patient. Cardioversion resulted in return to sinus rhythm without immediate complication in all patients. Thirteen patients had cerebral embolic events and four patients had peripheral embolism occurring 2 hours to 7 days after cardioversion. None of the patients were therapeutically anticoagulated at the time of embolism. New or increased left atrial spontaneous echo contrast was detected in four of the five patients undergoing repeat TEE after cardioversion including one patient with a new left atrial appendage thrombus. CONCLUSIONS Embolism may occur after cardioversion of atrial fibrillation in inadequately anticoagulated patients despite apparent exclusion of preexisting atrial thrombus by TEE. These findings suggest de novo atrial thrombosis after cardioversion or imperfect sensitivity of TEE for atrial thrombi and suggest that screening by TEE does not obviate the requirement for anticoagulant therapy at the time of and after cardioversion. A randomized clinical trial is needed to compare conventional anticoagulant management with a TEE-guided strategy including anticoagulation after cardioversion.

Cardioversion guided by transesophageal echocardiography: The ACUTE Pilot Study : A Randomized, controlled trial

A trial fibrillation is characterized by a lack of organized electrical and mechanical atrial activity that results in an irregular heartbeat and increased risks for congestive heart failure, thromboembolism, and death [1-3]. Since 1962, direct-current cardioversion has been used to restore sinus rhythm in patients with atrial fibrillation [4]. However, successful cardioversion, with the sudden resumption of sinus rhythm, is itself associated with an increased risk for embolic stroke, which can result when thrombi in the left atrial appendage are dislodged [5-12]. Transesophageal echocardiography (TEE) is an excellent method with which to detect thrombi in the left atrial appendage [13-19]. Its use has therefore been proposed as a way to allow cardioversion to be done earlier and more safely than would be possible with conventional therapy, which consists of a total of 7 weeks of treatment with warfarin [14-23]. Recent studies [15-19] indicate that TEE-guided cardioversion with short-term anticoagulation therapy may have several advantages over the conventional approach. These advantages include a decreased risk for embolism, which results from the avoidance of cardioversion in patients who have thrombi in the left atrial appendage [15]; a decreased risk for bleeding, which occurs because anticoagulation therapy can be briefer [19]; greater initial conversion to and long-term maintenance of sinus rhythm, which result from doing cardioversion earlier [18, 19]; and greater cost-effectiveness, which results from the decreased incidence of embolic stroke [17]. The ACUTE (Assessment of Cardioversion Using Transesophageal Echocardiography) Pilot Study was a multicenter, randomized clinical trial designed to compare TEE-guided cardioversion with conventional management of cardioversion in patients with atrial fibrillation who have cardioversion [19]. The study had two objectives: to assess the general feasibility of a TEE-guided approach to cardioversion and to determine the general safety of the TEE-guided approach by comparing its clinical outcome with those of conventional management. Methods Patient Selection Patients who were candidates for electrical cardioversion were eligible for inclusion if they had atrial fibrillation, or atrial flutter with a history of atrial fibrillation, lasting longer than 2 days. Patients were excluded if they had received anticoagulant therapy for more than 7 days, had required urgent cardioversion as a result of hemodynamic instability, had had a cardioembolic event within the previous month, had contraindications to TEE or warfarin, were women with childbearing potential in whom pregnancy could not be excluded, were unable to give informed consent, or were unable to return for a follow-up visit. Our study protocol was approved by the institutional review boards at all clinical sites, and all patients provided written informed consent in advance. Study Protocol Patients who met the inclusion criteria were randomly assigned to receive either a conventional or a TEE-guided approach to cardioversion. Randomization was done using presealed, opaque envelopes that were computer generated and distributed to each clinical site (Figure 1). Random assignments were stratified by site and were generated in blocks of six. Figure 1. The ACUTE (Assessment of Cardioversion Using Transesophageal Echocardiography) study protocol. The conventional approach to cardioversion was that recommended by the American College of Chest Physicians: 3 weeks of therapeutic warfarin therapy, then cardioversion, then 4 weeks of warfarin therapy, and then a follow-up examination at the end of the 4 weeks [23]. Prothrombin times were monitored regularly, and the target international normalized ratio (INR) was 2 to 3. If assigned to the TEE group, patients began receiving anticoagulation therapy at their initial visit. The goal was to have patients therapeutically anticoagulated (therapeutic anticoagulation was defined as a partial thromboplastin time 1.5 to 2.5 times control values or an INR of 2.0 to 3.0) at the time of and after the planned cardioversion, for a total of 4 weeks of therapy. The initial choice of antithrombotic agent was determined by whether the patient was an inpatient or an outpatient at the time of randomization: Heparin was used for inpatients; warfarin was administered to outpatients. Transesophageal echocardiography, with subsequent cardioversion within 24 hours, was then scheduled as soon as stable therapeutic anticoagulation was assured. For example, if a patient was hospitalized and intravenous heparin therapy was administered, TEE was done as soon as a stable therapeutic partial thromboplastin time could be documented (for 24 to 36 hours); subsequent cardioversion was done if the presence of a thrombus was excluded. A 4- to 5-day overlap of warfarin therapy and intravenous heparin therapy was often necessary to maintain adequate anticoagulation after cardioversion. If the patient was to be managed as an outpatient, warfarin therapy was initiated on the day of study enrollment, and TEE and subsequent possible cardioversion were scheduled for at least 5 to 7 days later. Again, cardioversion was done when the patient was therapeutically anticoagulated, and all patients received maintenance therapy with warfarin for 4 weeks after cardioversion [15]. In the TEE group, cardioversion was done immediately after or within 24 hours of TEE because of the potential for thrombus formation in the period between TEE and cardioversion. If thrombi were detected in the left or right atrial appendages or atrial cavities, cardioversion was postponed and the patient received warfarin therapy for 4 weeks. After 4 weeks, TEE was repeated and, if no thrombus was detected, cardioversion was done. If a thrombus was still present, another 4-week course of warfarin therapy was administered and cardioversion was not done [15]. Clinical Outcomes Our feasibility outcomes were frequency of cardioversion, frequency of cardioversion occurring as scheduled, time to cardioversion, and time to sinus rhythm. Our clinical safety outcomes were clinically apparent ischemic stroke, transient ischemic attack, systemic embolization, deaths related to cardioversion or episodes of bleeding, and detected episodes of clinical hemodynamic instability (worsening congestive heart failure or hypotension) that rendered the patient unable to complete the protocol. Other outcome variables were the prevalence of thrombi, the number of patients without thrombi who had early cardioversion, and the immediate and follow-up rhythms after cardioversion. These outcomes were assessed for as long as 4 weeks after cardioversion but for no longer than 8 weeks after randomization. In the patients who did not have cardioversion and who spontaneously reverted to sinus rhythm, the variables were assessed at 4 weeks after spontaneous reversion. Study Organization and Procedures The administrative organization of the pilot study is described in the Appendix. Echocardiographic Examination Conventional transthoracic echocardiography was done in both study groups using commercially available equipment. In the TEE group, TEE was done according to standard techniques using phased-array biplane or multiplane transducers [24-26]. Complete transesophageal echocardiographic examination was done, and special attention was paid to imaging the left and right atria and left and right atrial appendages to assess the presence or absence of thrombi and spontaneous echo contrast. Echocardiographic Data Analysis Two-dimensional directed M-mode transthoracic echocardiography was used to derive the left ventricular septal and posterior wall thicknesses and the end-diastolic, end-systolic, and left atrial dimensions. Ejection fraction was calculated using standard techniques [27, 28]. The maximal left atrial and right atrial areas were planimetered on-line, and the severity of mitral regurgitation was qualitatively graded from 0 to 4+ by using color-flow mapping [29]. A thrombus was considered to be present if a mass detected in the appendage or body of the atrium appeared to be distinct from the underlying endocardium, was not caused by pectinate muscles, and was detected in more than one imaging plane. The presence or absence of spontaneous echo contrast was analyzed and defined as dynamic intracavitary echoes with a characteristic swirling pattern distinct from artifact. The degree of spontaneous echo contrast was categorized independently as absent, mild, or severe [30, 31]. Quality Control Measures Standard definitions of echocardiographic measurements were available to all of the clinical centers as part of a pilot operations manual. Echocardiograms at each clinical center were interpreted locally by a single physician who was highly experienced in echocardiography. Videotapes that showed the results of the first five echocardiographic examinations and all videotapes that showed thrombi were forwarded from the clinical centers to a central laboratory and overread by three experienced reviewers for consensus [19]. Electrical Cardioversion Cardioversion was done by using the standard method of Lown and associates [4] with an initial energy of at least 40 J for atrial flutter and 200 J for atrial fibrillation. Statistical Analysis Summaries of clinical, echocardiographic, and outcome data are expressed as means or frequencies with 95% CIs. Data that were not normally distributed were log-transformed and presented as geometric means. Outcomes were compared for the TEE and conventional therapy groups, for patients with and without thrombus (in the TEE group only), and for patients in the TEE and conventional therapy groups who had cardioversion. These analyses were done using the t-test for independent groups for continuous variables and the Fisher exact test for categorical variables. StatXact (Cytel Software, Cambridge, Massachusetts) was used to compute binary CIs; SAS softwar

Hematologic correlates of left atrial spontaneous echo contrast and thromboembolism in nonvalvular atrial fibrillation

OBJECTIVES This study examined the relation between left atrial spontaneous echo contrast, hematologic variables and thrombo-embolism in patients with nonvalvular atrial fibrillation. BACKGROUND Left atrial spontaneous echo contrast is associated with left atrial stasis and thromboembolism in patients with nonvalvular atrial fibrillation. However, its hematologic determinants in patients with nonvalvular atrial fibrillation are unknown. METHODS Clinical, hematologic and echocardiographic variables were prospectively measured in 135 consecutive patients with nonvalvular atrial fibrillation undergoing transesophageal echocardiography. RESULTS Patients with left atrial spontaneous echo contrast (n = 74, 55%) had an increased fibrinogen concentration (p = 0.029), platelet count (p = 0.045), hematocrit (p = NS) and left atrial dimension (p = 0.005). Multivariate analysis showed that left atrial spontaneous echo contrast was independently related to hematocrit (odds ratio = 2.24, p = 0.002), fibrinogen concentration (odds ratio = 2.08, p = 0.008) and left atrial dimension (odds ratio = 1.90, p = 0.004) but not platelet count. It was also associated with left atrial thrombus (n = 15, p = 0.001) and with recent embolism (n = 40, p < 0.001). In 40 clinically stable outpatients without previous embolism, left atrial spontaneous echo contrast was significantly related to hematocrit (p = 0.005), fibrinogen concentration (p = 0.035) and left atrial dimension (p = 0.029) but not to coagulation factor VII, D-dimer, erythrocyte sedimentation rate, platelet count, plasma beta-thromboglobulin, plasma glycocalicin or glycocalicin index. CONCLUSIONS Left atrial spontaneous echo contrast in patients with nonvalvular atrial fibrillation is independently related to hematocrit, fibrinogen concentration and left atrial dimension, indicating a relatively hypercoagulable state in addition to stasis. These findings support the hypothesis that left atrial spontaneous echo contrast is due to erythrocyte aggregation. Hematologic factors may contribute to its association with thromboembolism.

Selection of Patients for Transesophageal Echocardiography After Stroke and Systemic Embolic Events: Role of Transthoracic Echocardiography

BACKGROUND AND PURPOSE This study examined whether patients suffering from stroke and other systemic embolic events may be selected for transesophageal echocardiography on the basis of clinical and transthoracic echocardiographic findings. METHODS We performed transthoracic and transesophageal echocardiography on 824 patients after stroke and other suspected embolic events. Patients were classified into group A if they were in sinus rhythm and had a normal transthoracic echocardiogram. Group B consisted of all other patients. Transesophageal echocardiographic findings of left atrial spontaneous contrast, left atrial thrombus, complex aortic atheroma, and interatrial septal anomalies were correlated with clinical and transthoracic echocardiographic results. RESULTS Transesophageal echocardiography detected at least one potential source of embolism in 399 patients (49%): spontaneous contrast in 214 patients (26%), left atrial thrombus in 54 (7%), complex atheroma in 111 (13%), and interatrial septal anomalies in 126 (15%). In group A (n = 236), only 3 (1%) had spontaneous contrast, 11 (4.6%) had complex atheroma, and none had left atrial thrombus. In group B (n = 588), 211 patients (36%, P < .001) had spontaneous contrast, 54 (9.2%, P < .001) had atrial thrombus, and 100 (17%, P < .001) had complex atheroma. Interatrial septal anomalies were detected in similar proportions of patients (18% in group A versus 14% in group B). Left atrial spontaneous echo contrast, thrombus, and complex atheroma were significantly more prevalent in older patients, but interatrial septal anomalies were more prevalent in younger patients irrespective of transthoracic echocardiographic findings. Multivariate analysis identified both an abnormal transthoracic echocardiogram and patient age to be independent predictors of transesophageal echocardiographic findings of left atrial spontaneous echo contrast, left atrial thrombus, or complex atheroma. CONCLUSIONS Transesophageal echocardiography has a low yield for left atrial spontaneous contrast, left atrial thrombus, or complex aortic atheroma in patients with normal transthoracic echocardiogram and sinus rhythm and in younger patients. Interatrial septal anomalies are more prevalent in younger patients. Transthoracic echocardiogram should be performed in patients after stroke or systemic embolic events as a noninvasive screening tool. We recommend transesophageal echocardiogram for patients with abnormal transthoracic echocardiogram and in younger patients when the finding of a patent foramen ovale may contribute to patient management.

Evaluation of transesophageal echocardiography before cardioversion of atrial fibrillation and flutter in nonanticoagulated patients

This study prospectively evaluated the role of transesophageal echocardiography (TEE) in screening for atrial thrombi before electrical cardioversion in 40 nonanticoagulated patients with nonvalvular atrial fibrillation (n = 33) or atrial flutter (n = 7). Transthoracic echocardiography did not detect atrial thrombus in any patient. TEE detected left atrial appendage thrombi in five patients (12%, p = 0.03), significantly associated with left ventricular systolic dysfunction (p = 0.02) and left atrial spontaneous echo contrast (p = 0.04). Cardioversion was cancelled in the five patients with thrombi and in two patients with spontaneous reversion before planned cardioversion. Cardioversion was successful in 25 (76%) of the 33 remaining patients. Cerebral embolism occurred 24 hours after successful cardioversion in one patient with atrial fibrillation and left ventricular dysfunction, who had left atrial spontaneous echo contrast, but no thrombus was detected by TEE before cardioversion. Repeat TEE after embolism showed a fresh left atrial appendage thrombus and increased left atrial spontaneous echo contrast. These results indicate that TEE improves the detection of left atrial appendage thrombi in candidates for cardioversion, in whom the procedure may be deferred. However, the exclusion by TEE of preexisting atrial thrombi before cardioversion does not eliminate the risk of embolism after cardioversion because of persistent atrial stasis and de novo thrombosis.

Should all patients undergo transesophageal echocardiography before electrical cardioversion of atrial fibrillation

The management of anticoagulant therapy in patients with atrial fibrillation undergoing electrical cardioversion remains controversial, largely because of inadequate studies demonstrating risk or benefit, a relatively inconvenient anticoagulation management strategy and the increasing use of transesophageal echocardiography. Recent investigations into the potential mechanisms involved in the development of thrombus and systemic embolism in patients undergoing electrical cardioversion of atrial fibrillation may provide insight into underlying predisposing factors, with subsequent modification of management strategies. Conventional wisdom suggests that preexisting thrombus is responsible for thromboembolic events after cardioversion. However, development of a thrombogenic milieu after cardioversion, particularly in the left atrial appendage, may also be an important predisposing factor. To protect against both potential mechanisms of embolization, these data support therapeutic anticoagulation for all patients with atrial fibrillation of > 2 days in duration from the time of, as well as after cardioversion for a total of 4 weeks, undergoing cardioversion, even in the absence of thrombus on echocardiography. Therefore, the role of transesophageal echocardiography in this setting should be to enable early cardioversion if atrial thrombus is excluded and to identify high risk patients with atrial thrombi so as to postpone cardioversion and avoid the risk of embolization. Ultimately, however, a controlled, randomized and prospective clinical trial will be required to compare conventional management with a transesophageal echocardiography-guided strategy.

Integrated backscatter for quantification of left atrial spontaneous echo contrast

OBJECTIVES This study was designed to develop a quantitative method of spontaneous echo contrast (SEC) assessment using integrated backscatter and to compare integrated backscatter SEC measurement with independent qualitative grades of SEC and clinical and echocardiographic predictors of thromboembolism. BACKGROUND Left atrial SEC refers to dynamic swirling smokelike echoes that are associated with low flow states and embolic events and have been graded qualitatively as mild or severe. METHODS We performed transesophageal echocardiography in 43 patients and acquired digital integrated backscatter image sequences of the interatrial septum to internally calibrate the left ventricular cavity and left atrial cavity under different gain settings. Patients were independently assessed as having no, mild or severe SEC. We compared intensity of integrated backscatter in the left atrial cavity relative to that in the left ventricular as well as to the independently assessed qualitative grades of SEC. Fourier analysis characterized the temporal variability of SEC. The integrated backscatter was compared with clinical and echocardiographic predictors of thromboembolism. RESULTS The left atrial cavity integrated backscatter intensity of the mild SEC subgroup was 4.7 dB higher than that from the left ventricular cavity, and the left atrial intensity of the severe SEC subgroup was 12.5 dB higher than that from the left ventricular cavity. The left atrial cavity integrated backscatter intensity correlated well with the qualitative grade. Fourier transforms of SEC integrated backscatter sequences revealed a characteristic dominant low frequency/high amplitude spectrum, distinctive from no SEC. There was a close relationship between integrated backscatter values and atrial fibrillation, left atrial size, left atrial appendage flow velocities and thrombus. CONCLUSIONS Integrated backscatter provides an objective quantitative measure of SEC that correlates well with qualitative grade and is closely associated with clinical and echocardiographic predictors of thromboembolism. The relationship between integrated backscatter measures and cardioembolic risk will be defined in future multicenter studies.

Resolution of left atrial spontaneous echocardiographic contrast after percutaneous mitral valvuloplasty: Implications for thromboembolic risk

Left atrial spontaneous echocardiographic contrast (SEC) is an important marker of increased thromboembolic risk in patients with mitral stenosis. To evaluate the effect of percutaneous transseptal mitral valvuloplasty (PTMV) on SEC, we performed transesophageal echocardiography 1 day before and 3 months after PTMV on 88 consecutive patients. SEC was present in 65 (74%) patients before PTMV and was associated with absence of moderate or severe mitral regurgitation (p = 0.01), a smaller valve area (p = 0.02), an older age (p = 0.04), and atrial fibrillation (p = 0.05). At 3 months, PTMV resulted in a mean absolute and relative increase in valve area of 0.54 +/- 0.36 cm2 and 53% +/- 43%, respectively. SEC resolved in 37 patients but persisted in 28 (32%) patients at the 3-month study. The absolute and relative increase of valve area and worsened mitral regurgitation after PTMV were predictors of resolution of SEC, with the relative increase in valve area being the only significant predictor on multivariate analysis. PTMV frequently results in resolution of SEC, which may have important implications in reducing the thromboembolic risk in these patients.