© 2004 by European Society of Cardiology
Copyright © 2003, The European Society of Cardiology
Prevalence of atrial thrombi in patients with atrial fibrillation/flutter and subtherapeutic anticoagulation prior to cardioversion
aUnità Operativa di Cardiologia, Ospedale Valduce, Como, Italy
bUnità Operativa di Neurologia, AO Ospedale Civile di Vimercate, Italy
Received 13 March 2003; received in revised form 17 June 2003; accepted after revision 26 June 2003.
* Corresponding author. Unità Operativa di Cardiologia, Ospedale Generale Valduce Via Dante, 11 22100 Como, Italy. Fax: +39-031-308-047. gcorr{at}iol.it
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Abstract |
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 Top Abstract 1 Methods2 Results3 DiscussionReferences |
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Aims: Thromboembolism may complicate electrical cardioversion (ECV) of atrial fibrillation/flutter (AF). The use of 3 weeks of warfarin before ECV results in a substantial reduction of thromboembolic complications. Nevertheless, in patients scheduled for ECV subtherapeutic INR levels are common. We sought to assess the prevalence and the predictors of atrial thrombi in patients affected with sustained AF in whom subtherapeutic INR values were detected in the 3 weeks preceding scheduled ECV.
Methods and results: Forty-one patients with persistent AF and 
3 weeks warfarin anticoagulation who exhibited subtherapeutic INR values in the last 3 weeks underwent a transoesophageal echocardiogram (TOE) before a scheduled ECV. A left atrial appendage (LAA) thrombus was diagnosed on TOE in four patients (9.8%). Patients with thrombus had lower INR values (1.45±0.09 vs 1.72±0.20; p = 0.0068), lower LAA emptying velocities (13.75±4.5 vs 25.86±12.4 cm/s; p = 0.0313) and higher prevalence of atrial smoke (100 vs 37.8%, p = 0.03).
Conclusions: Subtherapeutic levels of anticoagulation before elective ECV of AF may expose patients to post-ECV thromboembolic sequelae, especially in patients with lowest INR values. Current recommendations of a full course of therapeutic anticoagulation before ECV of persistent AF should be firmly observed.
Keywords: anticoagulation; echocardiography; fibrillation
In patients with atrial fibrillation and atrial flutter (AF) electrical cardioversion (ECV) is performed to relieve symptoms, improve cardiac mechanical function and possibly reduce embolic risk. Unfortunately, patients with sustained AF are subjected to a 5–7% risk of cardioversion-related thromboembolism if several weeks of anticoagulation are not prescribed before cardioversion.1–3 Stroke following ECV represents the most feared consequence of this therapy. Clinical thromboembolism after ECV of AF is related both to migration of atrial thrombi present at the time of cardioversion and to the de novo formation and migration of thrombi in the postcardioversion period.4 In an effort to reduce ECV-related thromboembolic risk current American College of Chest Physicians' (ACCP) guidelines recommend that all patients with AF for more than 2 days be treated with 3 weeks of therapeutic (INR
2) warfarin anticoagulation before ECV followed by 4 weeks of therapeutic anticoagulation after resumption of sinus rhythm.5 The pre-ECV period of warfarin treatment may promote silent resolution of pre-existing atrial thrombus; in the post-ECV period warfarin serves as prophylaxis of new thrombus formation.5 Nevertheless, recent reports have shown that anticoagulation guidelines are poorly followed in routine clinical practice, especially in the elderly.6,7 Furthermore, even among patients for whom prophylactic warfarin is intended, transient subtherapeutic INR values are common.8,9 An incomplete anticoagulation regimen could offer an inadequate prophylaxis against ECV-related thromboembolism. This investigation sought to assess the prevalence and the predictors of atrial thrombi in patients affected with persistent sustained AF who received warfarin for 3 weeks but had subtherapeutic INR values in the 3 weeks preceding scheduled ECV. |
1 Methods |
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1.1 Study population
We performed a retrospective chart review of all ECVs performed at the Ospedale Valduce's Cardiology Department between June 1999 and October 2002.
We identified 220 patients who underwent a transoesophageal echocardiography (TOE) to rule out intra-atrial thrombi before ECV of AF lasting longer than 2 days or of unknown duration. One hundred and eighty-nine patients underwent early TOE-guided ECV;9 in these patients TOE was done because of the short period of preliminary anticoagulation and were excluded from analysis.
The study group comprised 41 patients on prolonged (i.e. 3 weeks' duration) warfarin therapy who underwent TOE because of subtherapeutic (<2) INR values on at least one measurement in the last 3 weeks preceding the scheduled ECV. Baseline demographic information, clinical and echocardiographic variables and INR status were recorded. The median of INR measurements in the 3 weeks period before ECV was 5 (range 2–21). The lowest INR value detected in this period was used for statistical analysis.
1.2 Echocardiographic examination
Conventional transthoracic echocardiogram (TTE) was initially performed in all patients with commercial Philips Sonos 2000 or 5500 echocardiograph (Andover, Massachusetts) equipped with 2–2.5 MHz or 4s transducers. M-mode left atrial and left ventricular dimensions were measured in the parasternal long-axis view.10 Left ventricular fractional shortening was calculated as the difference between end diastolic dimension and end systolic dimension, divided by the end diastolic dimension.11 Left atrial antero-posterior diameter was measured. The 2-D apical four-chamber view was used to estimate left ventricular ejection fraction. TTEs were reviewed by three experienced echocardiographers (G.C., G.T., M.S.). All patients underwent TOE immediately before ECV. Warfarin dosage was adjusted when indicated; TOE and subsequent ECV were scheduled as soon as INR values were 2. TOE was done with commercial 3.7/5 MHz Philips omniplane probe. Patients received posterior pharyngeal anesthesia with 10% lidocaine spray and mild sedation with IV diazepam. The left atrial appendage (LAA) was initially viewed in the horizontal (0°) plane; multiplane imaging was done by rotating the imaging sector from 0° to 180° during continuous visualization of the appendage. An atrial thrombus was defined as a circumscribed and uniformly consistent echoreflective mass of different texture than atrial wall.12 Off-axis views of LAA were employed in order to differentiate thrombus from pectinate muscles.13 Spontaneous echocontrast (SEC), a marker of blood stasis, was considered present when dynamic ‘smokelike’ echoes were seen within the atria.14 LAA velocity profiles were obtained by pulsed-wave Doppler interrogation 1 cm within the orifice of the LAA.15 All TOEs were reviewed by one experienced echocardiographer (G.C.). In patients free from atrial thrombi ECV was done within 6 h after completion of TOE. Accordingly to current ACCP guidelines therapeutic anticoagulation was maintained for at least 4 weeks after restoration of sinus rhythm.5 In patients with TOE documented atrial clot ECV was cancelled and long-term anticoagulation was prescribed.
1.3 Statistical analysis
Comparisons were made with the Fisher's exact test for frequency data and with a t test for unpaired parametric data. A logistic regression analysis was performed. INR levels, prevalence of atrial SEC and LAA velocity profiles were considered potentially explanatory covariates in the LAA thrombus formation. A step-wise (step-down) regression strategy was used for variable selection. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. A significance test was made using Chi square test. A Hosmer Lemeshow goodness of fit test was performed to check for linearity on the log odds scale. All analysis were made using Stata 4.0 (Stata Corp.).
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2 Results |
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No atrial thrombus was seen in any patient on TTE. On TOE, an atrial thrombus was identified in four patients (9.8%) (Fig. 1); the clot was always confined to LAA. Baseline demographic, clinical and echocardiographic (TTE and TOE) data in patients with and without atrial thrombus are listed in Table 1. In comparison with the 37 patients without atrial thrombus the four patients with atrial thrombus exhibited lower INR values (1.45±0.09 vs 1.72±0.20; p = 0.0068), lower LAA emptying (13.75±4.5 vs 25.86±12.4 cm/s; p = 0.0313) and filling (13.75±10.4 vs 28.42± 14.9 cm/s; p = 0.0326) velocities (Fig. 1) and higher prevalence of atrial SEC (37.8 vs 100%, p = 0.03). Age, gender, arrhythmia type (atrial fibrillation vs atrial flutter) history of hypertension, use of digitalis, presence of structural heart disease, left ventricular fractional shortening and ejection fraction and left atrial diameter were not predictive of atrial thrombus. INR value and LAA emptying velocity were selected as relevant covariates in a logistic regression model of LAA thrombus formation. The OR of having an LAA thrombus, for 0.1 decrease in the INR value, was 2.42 (CI 0.99–5.94). The OR of having an LAA thrombus, for 1 cm/s decrease in the LAA emptying velocity, was 1.30 (CI 0.99–1.71).
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Follow-up median length after TOE was 12 months (range 1–39). In the group of 37 patients without atrial thrombus we detected a transitory ischemic attack (TIA) and no deaths. In the group of four patients with atrial thrombus on TOE we detected two TIAs, two major bleedings (one digestive bleeding which required blood transfusion and one cerebral haemorrhage), and two deaths.
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3 Discussion |
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TopAbstract1 Methods2 Results3 DiscussionReferences |
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In patients with AF lasting longer than 2 days current ACCP guidelines recommend therapeutic anticoagulation (target INR 2.5; range 2.0–3.0) for 3 weeks before and at least 4 weeks after elective ECV5 (conventional anticoagulation strategy). Alternatively, several authors have advocated the use of TOE to guide early ECV (TOE-guided strategy).4,9,16,17 In the TOE-guided ECV patients are treated with anticoagulation beginning at the time of TOE. ECV is performed if no thrombus is seen on preliminary TOE; in order to prevent new thrombus formation in the post-ECV period warfarin therapy should be maintained until normal sinus rhythm has been maintained for at least 4 weeks.9,16,17
Patients treated with conventional anticoagulation therapy (i.e., warfarin for 3 weeks) theoretically should undergo ECV without a preliminary TOE. Nevertheless, when INR levels are suboptimal before the scheduled ECV one may be worried about possible post-ECV thromboembolism. We thought that an incomplete course of therapeutic anticoagulation could lead to an inadequate prophylaxis against ECV-related thromboembolism. For this reason we decided to perform a TOE to rule out LAA thrombus before the planned ECV in patients anticoagulated for 3 weeks but who exhibited at least one subtherapeutic INR value in the last 3 weeks. Adopting this strategy we found a 9.8% prevalence of atrial thrombus in 41 patients. Lower INR values, the presence of SEC and of worse indices of LAA contractility were predictors for the presence of thrombus.
The relation between the intensity of anticoagulation and the risk of thromboembolism in chronic AF has been well documented.18 Furthermore, a recent retrospective study exhibited that thromboembolic complications of ECV were related to inadequate intensity of anticoagulation.19 The high prevalence of atrial thrombus in patients inadequately anticoagulated could contribute to explain the occurrence of ECV-related thromboembolism in these subjects. Since we did not perform ECV in our patients with atrial thrombus on TOE, we could not verify the true ECV-related embolic risk of this finding.
Atrial SEC (a marker of blood stasis) and low LAA emptying velocities on pulsed-wave Doppler interrogation are well-recognized markers of increased thromboembolic risk.20,21 Not surprisingly, the coexistence of lower INR values and of worse left atrial and appendage mechanical function identified in our study population a group of increased risk for the presence of atrial clot. Unfortunately, presence of smoke and of LAA dysfunction can be confidently detected only with TOE.
A recent study in a large series showed a 10% prevalence of atrial thrombus in patients with subtherapeutic INR values while taking conventional anticoagulation.22 These data appear to be similar to our findings and confirm the concern about post-ECV thromboembolism in inadequately anticoagulated patients.
Patients with atrial thrombi had more events (two TIAs and two major bleedings; two patients died) in comparison with patients without atrial thrombi (one TIA). Our data are in agreement with previously published papers which described an higher occurrence of events in patients with atrial thrombi on TOE.23
This study has several limitations. In a retrospective study it is not possible to characterize a cohort as accurately as in a randomized prospective trial. The lowest INR value in the last 3 weeks of anticoagulation could not accurately reflect the anticoagulation status in a given patient. Furthermore, warfarin management and INR checks were not standardized. However, the scenario of anticoagulation management solely through primary physician's office is common in clinical practice.
Our data support the concern for post-ECV thromboembolism when INR is subtherapeutic before the scheduled ECV. Current ACCP anticoagulation guidelines for elective ECV of AF2 days' duration should be firmly observed. In patients with subtherapeutic INR values in the pre-ECV period a strategy of increasing the warfarin dosage and restart the ‘3 weeks’ clock may be a reasonable approach. Alternatively, TOE should be done before ECV to rule out intra-atrial thrombus.
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Acknowledgements |
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We wish to thank Laura Zaffaroni, Mariangela Negretti and Livia Beretta for their dedicated technical assistance and help.
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