Background
Cardioversion (CV) and radiofrequency catheter ablation (RFA) are often used to restore sinus rhythm in patients with atrial fibrillation (AF). These procedures are associated with a risk for stroke. The use of transesophageal echocardiography (TEE) to guide the management of AF is a validated strategy for patients in whom CV is planned, as well patients before RFA. For patients in whom the initial procedure fails, repeat TEE is often performed before repeat CV or RFA. The aim of this study was to test the hypothesis that patients with initial negative results on TEE would be unlikely to have thrombi detected on subsequent TEE and thus may avoid repeat procedures.
Methods
A total of 2,999 patients with AF were identified via retrospective review who had undergone TEE before CV or RFA, and 418 of these individuals underwent repeat TEE. After excluding patients who underwent repeat TEE >365 days from the initial study ( n = 135) and those with thrombi on initial TEE ( n = 20), 263 patients who had underwent two or more examinations were identified and analyzed.
Results
Of 263 eligible patients, two (0.8%; 95% confidence interval, 0.21–2.7%) had thrombi on subsequent TEE.
Conclusions
Fewer than 1% of patients with AF with negative results on baseline TEE had thrombi detected on repeat TEE before subsequent CV or RFA. Thus, it may be possible to selectively screen patients to identify those at low risk for developing thrombi subsequent to negative results on initial TEE, especially if patients are in sinus rhythm. These results suggest the need for a prospective trial to definitively answer the question regarding repeat TEE in low-risk patients.
Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia. It has an overall prevalence of 1%, and approximately 2.3 million US adults currently have AF. This will likely increase to >5.6 million by 2050, with >50% of affected individuals aged ≥80 years, making it a significant public health issue. It is also a potent risk factor for ischemic stroke, increasing the risk for stroke fivefold. Symptomatic AF and atrial flutter (AFl) may also reduce quality of life and functional status. Both are associated with higher medical costs as well as an increased risk for death. Electrical cardioversion (CV) is often used to restore normal sinus rhythm (NSR) in patients with AF, but the procedure is associated with a risk for stroke, which may result if left atrial thrombi are dislodged when NSR is restored. Transesophageal echocardiography (TEE)–guided CV is a clinically validated strategy for patients in whom CV is planned to guide the management of AF or AFl. TEE is a semi-invasive and somewhat costly procedure with some inherent risks to patients.
Radiofrequency catheter ablation (RFA) is being used with increasing frequency to help restore or maintain NSR in patients with AF or AFl. Current clinical practice at many institutions is to perform TEE before RFA, even if the patient is in NSR. At many institutions, patients who undergo ablation have TEE first, irrespective of their rhythms, international normalized ratios (INR), or risk for thrombus. In addition, many patients, especially those with inadequate or uncertain anticoagulation status, undergo TEE before CV. This is often the case even in patients with prior preprocedural TEE.
It is imperative to risk-stratify patients before repeat CV or RFA. This requires judicious review of the patient’s medical history and underlying risk factors. With rising medical costs and the potential for adverse events with TEE, it is of interest to identify patients who can safely proceed to repeat CV or RFA without repeat TEE. Identifying low-risk patients with prior TEE who can safely proceed to repeat procedures without repeat TEE may reduce costs without compromising patient safety.
We hypothesized that individuals with negative results on initial TEE would be unlikely to have thrombi detected on subsequent TEE and thus may avoid repeat preprocedural TEE. In addition, we sought to determine if there were any clinical or echocardiographic parameters present at the time of initial TEE that would predict the formation of left atrial appendage (LAA) thrombus. We therefore retrospectively reviewed our experience to determine the incidence of thrombus detection in patients with initial negative results.
Methods
Study Population
We conducted a retrospective review of patient data at The Ohio State University Medical Center, which was approved by The Ohio State University institutional review board. We identified 2,999 patients from 2000 to 2009 (using The Ohio State University’s Information Warehouse database with the specific query “atrial fibrillation/flutter pre-cardioversion/rule out thrombus”) who underwent TEE for AF or AFl before CV or RFA. We analyzed all patients who underwent two or more preprocedural transesophageal echocardiographic exams for AF or AFl ( n = 418). We excluded those who underwent repeat TEE >365 days from the index exam ( n = 135) and those who had thrombi on their initial exams ( n = 20). We thus identified 263 patients who had at least two transesophageal echocardiographic studies, of which the results of the first were negative for thrombus. These patients underwent initial TEE immediately before CV or RFA. Their second (and subsequent) exams were performed before repeat CV or RFA procedures. The remaining 2,581 patients who did not undergo repeat TEE had only a single CV or RFA procedure. We included all patients who met our initial inclusion criteria irrespective of valvular disease to assess the overall incidence observed in our TEE laboratory. Although valve disease makes it less likely that repeat TEE could be avoided, we assessed the thrombus risk for all individuals. We also performed a random 1-year sample of our database to determine the incidence of left atrial thrombus.
Clinical Data
We retrospectively calculated a clinically validated stroke risk index, the CHADS 2 score, for each patient on the basis of clinical data available at the time of index TEE. The CHADS 2 score ranges from 0 to 6 and is calculated as follows: 1 point for congestive heart failure; 1 point for hypertension; 1 point for age ≥ 75 years; 1 point for diabetes; and 2 points for history of stroke, cerebrovascular accident, transient ischemic attack, or systemic embolism. We also calculated (retrospectively) a more recent stroke risk stratification schema, the CHA 2 DS 2 -VASc score (1 point for cardiac failure or dysfunction, 1 point for hypertension, 2 points for age ≥ 75 years, 1 point for diabetes, 2 points for stroke, 1 point for vascular disease or history of myocardial infarction, 1 point for age 65–74 years, and 1 point for sex category [female]), again on the basis of clinical data available at the time of initial TEE. The score ranges from 0 to 9, and a score ≥ 2 identifies those at high risk for thromboembolic events. Low thromboembolic risk is defined as a CHADS 2 or CHA 2 DS 2 -VASc score of 0 or 1, and high-risk patients have scores ≥ 2. We compared high-risk and low-risk groups using both risk stratification schemes. We also performed a direct comparison between high-risk CHADS 2 and CHA 2 DS 2 -VASc groups. The INR was recorded at the time of TEE and <30 days before the procedure if available.
We assessed the incidence of thrombus on the first subsequent follow-up transesophageal echocardiographic exam in patients who met inclusion criteria. Two investigators (D.A.O. and S.A.S.) reviewed all repeat exams with positive findings. We excluded four patients who demonstrated thrombi on device wires ( n = 3) on repeat TEE or at the septal perforation site ( n = 1), as this is a separate physiologic process from thrombus formation in the LAA. Thrombi on the device wires did not preclude proceeding to RFA or CV. One patient with a thrombus on the right atrial side of the interatrial septum at the site of a previous septal perforation had CV delayed by 4 weeks. LAA thrombus was defined as a mass adherent to the wall of the LAA displaying either independent motion or different echogenic density.
We further compared patients in NSR with those in AF or AFl at the time of their repeat studies to assess the role this may have played with regard to new spontaneous echocardiographic contrast (SEC) formation. We also evaluated the time interval to repeat TEE for all patients and within the subgroups of NSR and AF or AFl.
Echocardiographic Data
Standard techniques were used to perform TEE. Specifically, level 2 and 3 echocardiographers followed the laboratory protocol using a Philips multiplane probe (Philips Medical Systems, Andover, MA). Covariates of interest included left atrial size > 4.5 cm (because this is known to affect the success of CV), the degree of valvular heart disease (defined as negative if no disease or mild stenosis or regurgitation and as positive if more than mild stenosis or regurgitation), the presence of SEC, LAA velocity, and left ventricular ejection fraction (LVEF). Left atrial enlargement was determined from clinical reports using a left atrial anteroposterior diameter > 45 mm. The severity of valvular disease was defined by clinical reports and semiquantitated by the individual reader. SEC was defined as swirling patterns of echogenicity in the left atrium and LAA distinct from white-noise artifact. We did not quantify the severity of SEC. We graded SEC indicated in clinical reports as either present or absent, reducing the potential for interobserver variability. LVEF was determined using the most recent transthoracic echocardiographic report available. If no transthoracic echocardiogram was available, LVEF from the transesophageal echocardiographic report was used. LVEF was determined by the individual reader using semiquantitated methods by means of visual estimation or the biplane Simpson’s method in those studies with adequate volumetric measures. LAA velocity was also determined from clinical reports.
Statistical Analysis
Study data were stored in the Research Electronic Data Capture database, an electronic data capture tool hosted at The Ohio State University. Research Electronic Data Capture is a secure, Web-based application designed to support data capture for research studies.
Continuous data are presented as mean ± SD. Continuous variables were assessed for normality and were compared using Student’s t tests. Categorical variables were analyzed using contingency tables and McNemar’s test statistic with Yates’s correction for continuity. Values resulting in P < .05 were deemed statistically significant. Statistical calculations were performed using JMP version 8.0 (SAS Institute Inc., Cary, NC).
Results
Patient Demographics and Clinical Characteristics
The incidence of left atrial thrombus on initial TEE before CV or RFA for patients in AF was 7% (29 of 423). Our study population included 263 patients, with the majority being Caucasian men (see Table 1 ). The mean age was 59 ± 11 years. The average number of repeat transesophageal echocardiographic exams was 1.8 (range, 1–8; Figure 1 ). Of the 263 patients, 76% had one repeat study, 15% had two repeat studies, and 9% had three or more repeat studies. The mean interval until the first repeat study was 130 ± 99 days. We found no differences ( P > .05) between baseline and repeat TEE in terms of LVEF, the percentage of patients in NSR, the presence of SEC, or LAA velocity ( Table 2 ). Two thirds of patients were in AF or AFl. The average INR at the time of initial TEE was 1.69 ± 0.65 and was higher (1.83 ± 0.61) at the time of repeat TEE ( P < .0099; Table 2 ). There were 107 patients (41%) with some degree of valve disease (greater than mild valvular regurgitation or stenosis). With regard to “high-risk” patients (patients with valve disease that increased their risk for a thromboembolic event), 2.8% of those with valve disease had mechanical mitral valve replacement, 0.9% had bioprosthetic mitral valves, 2.8% had mechanical aortic valve replacement, 3.7% had bioprosthetic aortic valves, 0.9% had bioprosthetic tricuspid valves, and 3.7% had mitral stenosis. Collectively, 15% of the patients with valve disease were particularly high risk patients.
| Variable | Value |
|---|---|
| Age (y) | 59 ± 11 |
| Men | 66% |
| Caucasian | 95% |
| Diabetes mellitus | 23% |
| Hypertension | 64% |
| Cerebrovascular accident or transient ischemic attack | 6% |
| Congestive heart failure | 28% |
| History of myocardial infarction or vascular disease | 35% |
| Interval to repeat TEE (d) | 130 ± 99 |
| CHADS 2 score | 1.33 ± 1 |
| CHA 2 DS 2 -VASc score | 2.30 ± 1.5 |
| Variable | At baseline TEE | At repeat TEE | P |
|---|---|---|---|
| LVEF (%) | 49.9 ± 13 | 48.8 ± 13 | .0512 |
| INR | 1.69 ± 0.65 | 1.83 ± 0.61 | .0099 ∗ |
| Sinus rhythm | 37% | 35% | .6477 |
| SEC | 32% | 35% | .3329 |
| LAA velocity (cm/sec) | 41.3 ± 20 | 42.3 ± 20 | .6333 |
Clinical Outcomes
Of the 263 patients, only two (0.8%; 95% confidence interval, 0.21–2.7%) underwent repeat TEE with positive results for thrombus formation. In both patients, the thrombus was identified in the LAA ( Figure 2 ). Both individuals were in AF and also had SEC and left atrial enlargement during their baseline studies. LVEFs at the time of repeat TEE were 20% for both patients. One patient had a subtherapeutic INR of 1.9 at the time of repeat TEE. The INR was 2.2 in the other individual. Neither patient had a therapeutic INR during the 30 days before repeat TEE. Their CHADS 2 scores were 1 and 3, respectively, and their CHA 2 DS 2 -VASc scores were 2 and 6 ( Tables 3 and 4 ).
| Patient | Rhythm at repeat TEE | SEC | Age (y) | Baseline LVEF (%) | Repeat LVEF (%) | Baseline INR | Repeat INR | Therapeutic INR for 30 d before repeat TEE | CHADS 2 score (range, 0–6) | CHA 2 DS 2 -VASc score (range, 0–9) | Interval to repeat TEE (d) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | AF | Yes | 70 | 15 | 20 | 1.1 | 1.9 | No | 1 | 2 | 56 |
| 2 | AF | Yes | 56 | 55 | 20 | 1.1 | 2.2 | No | 3 | 6 | 19 |
| Patient | Age (y) | Sex | Rhythm on repeat TEE | Thrombus | Baseline LVEF (%) | Repeat LVEF (%) | INR | CHA 2 DS 2 -VASc (range, 0–9) | CHADS 2 score (range, 0–6) | SEC | LAA velocity (cm/sec) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 67 | Male | NSR | No | NA | 55 | 2.1 | 3 | 2 | Yes | 32 |
| 2 | 68 | Male | AF/AFl | No | 40 | 50 | 3.2 | 5 | 3 | Yes | 40 |
| 3 | 55 | Female | NSR | No | 40 | 20 | 2.2 | 3 | 2 | Yes | NA |
| 4 | 63 | Male | AF/AFl | No | 45 | 45 | 2.0 | 3 | 2 | Yes | 26 |
| 5 | 51 | Female | NSR | No | 35 | 55 | 2.5 | 1 | 0 | No | 40 |
| 6 | 68 | Male | AF/AFl | No | 60 | 60 | 2.8 | 2 | 1 | No | 35 |
| 7 | 55 | Male | AF/AFl | No | 55 | 40 | 2.2 | 1 | 1 | No | 80 |
| 8 | 55 | Male | NSR | No | 60 | 60 | 2.8 | 2 | 1 | No | 45 |
| 9 | 39 | Male | AF/AFl | No | 25 | 25 | 2.3 | 1 | 1 | No | 30 |
Many patients in our study (61%) had INRs < 2 at the time of repeat TEE ( Figure 3 ). Of the 102 patients with INRs > 2 at the time of repeat TEE, data were not available for 80 patients regarding their anticoagulation status for the preceding 30 days. Twenty-two patients had INR data for the 30 days before repeat TEE, and only nine had therapeutic INRs ( Figure 3 ). None of these individuals had thrombi on repeat TEE ( Tables 3 and 4 ).
