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Left atrial thrombus, transient ischemic attack, and atrial fibrillation: Does left atrial thrombus predict? Does absence protect?
Editorial
Left atrial thrombus, transient ischemic attack, and atrial fibrillation: Does left atrial thrombus predict? Does absence protect? Richard G. Sheahan, MD Chapel Hill, NC
See related article on page 676.
O body swayed to music, o brightening glance, How can we know the dancer from the dance? William Butler Yeats1 Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance. As our population ages, the prevalence of AF increases.2 Sustained AF results in hemodynamic impairment and impaired quality of life3,4 but the dreaded and disabling consequences of thromboembolic events also contribute to the increased morbidity and mortality associated with AF.5,6 The first report of left atrial (LA) thrombus was published in 1809.7 In 1933, the observation that AF in the presence of rheumatic mitral valve disease predisposed patients to LA thrombi and systemic embolism was published.8 However, it was not until more than 3 decades later that nonrheumatic AF was recognized as a powerful risk factor for stroke, accounting for 15% of all ischemic strokes.9,10 Autopsy series confirmed a high frequency of LA thrombus and systemic embolism in patients with nonvalvular AF.9-11 Whether AF reflects a systemic hypercoagulable state has not been clearly established.12-14 Approximately 35% of patients with nonrheumatic AF will sustain a stroke within 10 years.15 Patients with nonrheumatic AF and a prior minor stroke or transient ischemic attack (TIA) are at risk for developing a recurrent stroke.16 Pooled data from primary prevention trials showed that stroke or TIAs were independent risk factors for stroke.15 In 1972, Fisher suggested that stroke could be prevented in patients with AF with the use of warfarin anticoagulation before the first thromboembolic event.17 Since then, warfarin has been shown to prevent ischemic strokes caused by AF.15
From the Division of Cardiology, University of North Carolina, Chapel Hill, NC. Reprint requests: Richard G. Sheahan, MD, Associate Professor of Medicine, Director, Electrophysiology Laboratory, Division of Cardiology, 324 Burnett-Womack Building, University of North Carolina, Chapel Hill, NC 27599-7075. E-mail: [email protected] Am Heart J 2003;145:582-5. Copyright 2003, Mosby, Inc. All rights reserved. 0002-8703/2003/$30.00 ⫹ 0 doi:10.1067/mhj.2003.92
With the introduction of transthoracic echocardiography, the pursuit of risk marker identification began. Echocardiographic parameters predictive of stroke included left ventricular dysfunction and LA size.18 In the Framingham study, of subjects aged 50 years or older, those with the largest left atrium were more likely in follow-up to have a stroke develop.19 Transesophageal echocardiography (TEE) provides superior visualization of the left atrium, particularly the LA appendage. Patients with newly diagnosed AF in the setting of acute thromboembolism have a much higher prevalence of residual LA thrombi.20 TEE showed that 15% of patients with AF for longer than 48 hours had evidence of atrial thrombus; 80% were in the left atrium.21 The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study reported the presence of thrombus in 13.8% of the patients undergoing TEE in a group of patients with AF for longer than 2 days who were not previously anticoagulated.22 Manning et al21 showed that after prolonged anticoagulation, 18 of 34 patients underwent an uneventful cardioversion, with most undergoing a repeat TEE before cardioversion. After a median of 4 weeks of anticoagulation, a repeat TEE showed that 89% of atrial thrombi had resolved.23 No new thrombi were identified and no clinical thromboembolic events occurred, confirming thrombus resolution and prevention of new thrombus formation.23 In recent years, the role of the TEE has become pivotal in the early management of newly diagnosed patients.22 TEE has allowed for the convenient and early detection of LA thrombus. Thus, a negative TEE for thrombus allows for the safe and early restoration of sinus rhythm in the symptomatic patient.22 The visualization of spontaneous echo contrast (SEC) or “smoke” within the body of the left atrium is believed to represent erythrocyte aggregation in low sheer rate conditions.24 SEC is a marker for LA stasis and increased LA thrombogenicity25 and was found to be associated with both LA thrombus26 and thromboembolism.27-29 However, SEC may be seen in ⬎50% of patients with AF and in ⬎80% of patients with AF and LA appendage thrombi.21,30 In this issue of the Journal, Stoddard et al31 report on their findings from a prospective observational study of patients with AF of at least 4 days duration
American Heart Journal Volume 145, Number 4
who underwent a TEE at a single center. This study demonstrated an association between left atrial thrombus and TIA in patients with AF. Patients with prosthetic aortic or mitral valves, an estimated life expectancy of ⬍3 months, or atrial flutter at the time of enrollment were excluded. After a TEE was performed, 261 of 272 (96%) patients were followed up for a mean of 2.5 years. Follow-up data could not be obtained on 11 patients. The end points included TIA, stroke, peripheral embolism, or death. Left atrial thrombus was detected in 46 (17.6%) of 261 patients, predominately (43/46) isolated to the left atrial appendage. This prevalence was higher than the 13.8% observed in the larger ACUTE study.22 LA SEC was observed in 131 (50%) patients, similar to other studies.21,30 Of the 19 patients who had a TIA, significantly more occurred in patients with (10/46, 21.7%) than without (9/215, 4.2%) an LA thrombus. Combined embolic events occurred more frequently in patients with LA thrombus (15/46, 32.6% vs 28/215, 13%). Patients with an LA thrombus were more likely to be taking warfarin (76% vs 50%) and less likely to be using aspirin (26% vs 44%), compared with those patients without LA thrombus. Those patients with an LA thrombus had greater LA diameters (51.3 mm vs 44.3 mm), higher frequencies of persistent AF (91% vs 67%), lower left ventricular ejection fractions (41% vs 49%), and higher frequencies of LA SEC (72% vs 46%) than the patients without an LA thrombus. The presence of LA SEC and LA thrombus was similar to previously reported studies.21,30 For the entire group, multivariate logistic regression analysis showed congestive heart failure at baseline as the only independent predicator of TIA during follow-up (odds ratio 2.7). With the addition of TEE variables, LA thrombus was the only independent predicator of TIA (odds ratio 7.7). The TIA event rates were 9.2% per year with LA thrombus versus 1.9% without. The embolic events were 13.8% per year and 5.1% per year, respectively. With the exception of a more frequent history of stroke, TIA, or both (10/10 vs 14/36), patients with LA thrombus who had a TIA during follow-up did not differ in frequency of warfarin or aspirin usage in, respectively, congestive heart failure, mitral stenosis, or hypertension. Of note, 46 of 46 with and 201 of 215 without a thrombus were in AF during follow-up. In a subgroup of 203 patients without LA thrombus or mitral stenosis, LA SEC was the only independent predicator of subsequent TIA (odds ratio 4.9). Death rates during follow-up did not differ: 17.5% versus 13.3%. The death rates serve as a reminder that patients with AF have increased mortality.5,6 A rigorous and precise antiembolic strategy was not used in this study. Patients with LA thrombus had TIA develop even though many were identified as taking warfarin. This suggests that either the anticoagulation
Sheahan 583
was subtherapeutic—INR ⬍2.0 — or the therapeutic INR range for those patients with LA thrombus is inadequate. Of the 46 patients with LA thrombus, more than half had a history of stroke or TIA.31 Perhaps a randomized clinical trial comparing standard INR with a higher INR therapeutic range should be considered in patients identified with LA thrombus who are at a higher risk for ischemic stroke. The presence of LA SEC identified patients with a trend for a higher embolic event rate, but the wide confidence intervals associated with LA SEC as a predictor of TIA suggest that SEC may be more of a marker for stasis rather than for embolism. Sinus rhythm does not protect against stroke, as confirmed by the preliminary results from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial.32 This rhythm versus rate control study did not show a decreased stroke risk in those patients who were maintained in sinus rhythm.32 However, most strokes in both groups occurred in patients not taking warfarin or with a subtherapeutic INR.32 Is it possible that some of the embolic events in this study were noncardioembolic TIA or stroke? Observations on ischemic strokes from the Stroke Prevention in AF I-III clinical studies suggest that most ischemic strokes in AF patients are probably cardioembolic, and these are reduced by adjusted-dose warfarin.33 Aspirin in AF patients appeared to primarily reduce noncardioembolic strokes.33 Implications suggest that aspirin be considered in at-risk patients to prevent nonischemic strokes. The lipid profiles of these patients were not included. Statin therapy has been shown to decrease the risk of ischemic stroke in patients with established coronary artery disease.34,35 Nonarrhythmic primary and secondary risk factor modification also needs to be considered in these older at-risk populations.36,37 At present, there are few options for patients who cannot take warfarin. However, there may be hope on the horizon. The use of the percutaneous left atrial appendage transcatheter occlusion device (PLAATO) to prevent stroke in high-risk patients with AF who are poor candidates for long-term warfarin therapy was shown to be feasible in humans.38 One-month TEE revealed continued stable implant position with smooth atrial-facing surface and no evidence of thrombus.38 The PLAATO approach, if the data are replicated in randomized clinical trials, has the potential to be used in those patients who cannot take warfarin. Stoddard et al31 showed that more than half the patients who had an LA thrombus had a history of stroke or TIA, and many had a subsequent embolic event. These very-high-risk patients with LA thrombus should be considered for a randomized trial comparing the PLAATO approach with conventional warfarin therapy after thrombus resolution.
American Heart Journal April 2003
584 Sheahan
This study reinforces the message that the dance is real, that AF and LA thrombus lead to TIAs. However, those with a negative TEE and AF are still at substantial risk for developing an embolic event—5.1% per year31—similar to the anticipated event rate.39 The current goal for high-risk patients is to carefully monitor and maintain the INR between 2 to 3.15,16,39 With aging or the onset of new cardiac comorbidities, patients who were once considered low risk for the development of thromboembolism transition to a higher risk profile. Now that the dance has been identified, the search to protect the dancer must proceed.
References 1. Yeats WB. Among school children. The Tower. 1928. 2. Benjamin EJ, Levy D, Vaziri EM, et al. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham Heart Study. JAMA 1994;271:840-4. 3. Dorian P, Paquette M, Newman D, et al. Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation. Am Heart J 2002;143:984-90. 4. Savelieva I, Paquette M, Dorian P, et al. Quality of life in patients with silent atrial fibrillation. Heart 2001;85:216-7. 5. Kannel WB, Abbott RD, Savage DD, et al. Coronary artery disease and atrial fibrillation: The Framingham Study. Am Heart J 1983;106:389-96. 6. Krahn AD, Manfreda J, Tate RB, et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-up Study. Am J Med 1995;98:476-84. 7. Burns A. Observations on formation of polypi of the heart. In: Diseases of the Heart. Edinburgh: Bryce; 1809. 8. Weiss S, Davis D. Rheumatic heart disease. III. Embolic manifestations. Am Heart J 1933;9:45-52. 9. Aberg H. Atrial fibrillation. I. A study of atrial thrombosis and systemic embolism in a necropsy material. Acta Med Scand 1969; 185:373-9. 10. Hinton RC, Kistler JP, Fallon JT, et al. Influence of etiology of atrial fibrillation on incidence of systemic embolism. Am J Cardiology 1977;40:509-13. 11. Lie JT. Atrial fibrillation and left atrial thrombus: an insufferable odd couple. Am Heart J 1988;116:1374-7. 12. Gustafsson C, Blomback M, Britton M, et al. Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. Stroke 1990;21:47-51. 13. Lip GYH. Does atrial fibrillation confer a hypercoagulable state? Lancet 1995;346:1313-4. 14. Mitusch R, Siemens HJ, Garbe M, et al. Detection of a hypercoagulable state in nonvalvular atrial fibrillation and the effect of anticoagulant therapy. Thrombos Haemost 1996:75:219-23. 15. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Arch Intern Med 1994;154:1449-57. 16. European Atrial Fibrillation Trial Study Group (EAFT). Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993;342:1255-62. 17. Fisher CM. Treatment of chronic atrial fibrillation. Lancet 1972;1: 1284. 18. The Stroke Prevention in Atrial Fibrillation Investigators. Predictors
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34. 35.
36.
of thromboembolism in atrial fibrillation: II. Echocardiographic features of patients at risk. Ann Intern Med 1992;116:6-12. Benjamin EJ, D’Agostino RB, Belanger AJ, et al. Left atrial size and the risk of stroke and death: the Framingham Heart Study. Circulation 1995;92:835-41. Manning WJ, Silverman DI, Keighley KS, et al. Prevalence of residual left atrial thrombi among patients with acute thromboembolism and newly recognized atrial fibrillation. Arch Intern Med 1995;1555:2193-7. Manning WJ, Silverman DI, Keighley CS, et al. Transesophageal echocardiographically facilitated early cardioversion from atrial fibrillation using short-term anticoagulation: final results of a prospective 4.5 year study. J Am Coll Cardiol 1995;25:1354-61. Klein AL, Grimm RA, Murray RD, et al. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001;344:1411-20. Collins LJ, Silverman DI, Douglas PS, et al. Cardioversion of nonrheumatic atrial fibrillation: reduced thromboembolic complications with 4 weeks of precardioversion anticoagulation are related to atrial thrombus resolution. Circulation 1995;92:160-3. Black IW, Hopkins AP, Lee LC, et al. Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. J Am Coll Cardiol 1991;18:398-404. Shively BK, Gelgand EA, Crawford MH. Regional left atrial stasis during atrial fibrillation and flutter: determinants and relation to stroke. J Am Coll Cardiol 1996;27:1722-9. Manning WJ, Weintraub RM, Waksmonski CA, et al. Accuracy of transesophageal echocardiography for identifying left atrial thrombi: a prospective, intraoperative study. Ann Intern Med 1995;123: 817-22. Daniel WG, Nellessen 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. Black IW, Chesterman CN, Hopkins AP, et al. Hematologic correlates of left atrial spontaneous echo contrast and thromboembolism in nonvalvular atrial fibrillation. J Am Coll Cardiol 1993;21:451-7. Leung DY, Black IW, Cranney GB, et al. Prognostic implications of left atrial spontaneous echo contrast in nonvalvular atrial fibrillation. J Am Coll Cardiol 1994;24:753-63. Manning WJ, Silverman DI, Gordon SP, et al. Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. N Engl J Med 1993;328:750-7. Stoddard MF, Singh P, Dawn B, et al. Left atrial thrombus predicts transient ischemic attack in patients with atrial fibrillation. Am Heart J 2002;145:676-82. Wyse DG for the AFFIRM Investigators. Late-breaking clinical trials I: survival in patients presenting with atrial fibrillation: the atrial fibrillation follow-up investigation of rhythm management. J Am Coll Cardiol 2002;40:6-7. Hart RG, Pearce LA, Miller VT, et al. Cardioembolic vs noncardioembolic strokes in atrial fibrillation: frequency of antithrombotic agents in stroke prevention in atrial fibrillation studies. Cerebrovasc Dis 2000;10:39-43. Vaughan CJ, Delanty N, Basson CT. Statin therapy and stroke prevention. Curr Opin Card 2001;16:219-24. Byington RP, Davis BR, Plehn JF, et al. Reduction of stroke events with pravastatin: the Prospective Pravastatin Pooling (PPP) Project. Circulation 2001;103:387-92. Yusuf S, Sleight P, Pongue J, et al. Effects of an angiotensin-con-
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verting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:145-53. 37. Smith SC Jr, Blair SN, Bonow RO, et al. AHA/ACC guidelines for preventing heart attack and death in patients with atherosclerotic cardiovascular disease: 2001 update. J Am Coll Cardiol 2001;38: 1581-3.
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38. Sievert H, Lesh MD, Trepels T, et al. Percutaneous left atrial appendage transcatheter occlusion (PLAATO) to prevent stroke in high-risk patients with atrial fibrillation: early clinical experience. Circulation 2002;105:1887-9. 39. Fuster V, Ryden LE, Asinger RW, et al. ACC/AHA/ESC guidelines for the management of patients with atrial fibrillation: executive summary. Circulation 2001;104:2118-50.
Left atrial thrombus, transient ischemic attack, and atrial fibrillation: Does left atrial thrombus predict? Does absence protect? Richard G. Sheahan, MD Chapel Hill, NC
See related article on page 676.
O body swayed to music, o brightening glance, How can we know the dancer from the dance? William Butler Yeats1 Atrial fibrillation (AF) is the most common sustained cardiac rhythm disturbance. As our population ages, the prevalence of AF increases.2 Sustained AF results in hemodynamic impairment and impaired quality of life3,4 but the dreaded and disabling consequences of thromboembolic events also contribute to the increased morbidity and mortality associated with AF.5,6 The first report of left atrial (LA) thrombus was published in 1809.7 In 1933, the observation that AF in the presence of rheumatic mitral valve disease predisposed patients to LA thrombi and systemic embolism was published.8 However, it was not until more than 3 decades later that nonrheumatic AF was recognized as a powerful risk factor for stroke, accounting for 15% of all ischemic strokes.9,10 Autopsy series confirmed a high frequency of LA thrombus and systemic embolism in patients with nonvalvular AF.9-11 Whether AF reflects a systemic hypercoagulable state has not been clearly established.12-14 Approximately 35% of patients with nonrheumatic AF will sustain a stroke within 10 years.15 Patients with nonrheumatic AF and a prior minor stroke or transient ischemic attack (TIA) are at risk for developing a recurrent stroke.16 Pooled data from primary prevention trials showed that stroke or TIAs were independent risk factors for stroke.15 In 1972, Fisher suggested that stroke could be prevented in patients with AF with the use of warfarin anticoagulation before the first thromboembolic event.17 Since then, warfarin has been shown to prevent ischemic strokes caused by AF.15
From the Division of Cardiology, University of North Carolina, Chapel Hill, NC. Reprint requests: Richard G. Sheahan, MD, Associate Professor of Medicine, Director, Electrophysiology Laboratory, Division of Cardiology, 324 Burnett-Womack Building, University of North Carolina, Chapel Hill, NC 27599-7075. E-mail: [email protected] Am Heart J 2003;145:582-5. Copyright 2003, Mosby, Inc. All rights reserved. 0002-8703/2003/$30.00 ⫹ 0 doi:10.1067/mhj.2003.92
With the introduction of transthoracic echocardiography, the pursuit of risk marker identification began. Echocardiographic parameters predictive of stroke included left ventricular dysfunction and LA size.18 In the Framingham study, of subjects aged 50 years or older, those with the largest left atrium were more likely in follow-up to have a stroke develop.19 Transesophageal echocardiography (TEE) provides superior visualization of the left atrium, particularly the LA appendage. Patients with newly diagnosed AF in the setting of acute thromboembolism have a much higher prevalence of residual LA thrombi.20 TEE showed that 15% of patients with AF for longer than 48 hours had evidence of atrial thrombus; 80% were in the left atrium.21 The Assessment of Cardioversion Using Transesophageal Echocardiography (ACUTE) study reported the presence of thrombus in 13.8% of the patients undergoing TEE in a group of patients with AF for longer than 2 days who were not previously anticoagulated.22 Manning et al21 showed that after prolonged anticoagulation, 18 of 34 patients underwent an uneventful cardioversion, with most undergoing a repeat TEE before cardioversion. After a median of 4 weeks of anticoagulation, a repeat TEE showed that 89% of atrial thrombi had resolved.23 No new thrombi were identified and no clinical thromboembolic events occurred, confirming thrombus resolution and prevention of new thrombus formation.23 In recent years, the role of the TEE has become pivotal in the early management of newly diagnosed patients.22 TEE has allowed for the convenient and early detection of LA thrombus. Thus, a negative TEE for thrombus allows for the safe and early restoration of sinus rhythm in the symptomatic patient.22 The visualization of spontaneous echo contrast (SEC) or “smoke” within the body of the left atrium is believed to represent erythrocyte aggregation in low sheer rate conditions.24 SEC is a marker for LA stasis and increased LA thrombogenicity25 and was found to be associated with both LA thrombus26 and thromboembolism.27-29 However, SEC may be seen in ⬎50% of patients with AF and in ⬎80% of patients with AF and LA appendage thrombi.21,30 In this issue of the Journal, Stoddard et al31 report on their findings from a prospective observational study of patients with AF of at least 4 days duration
American Heart Journal Volume 145, Number 4
who underwent a TEE at a single center. This study demonstrated an association between left atrial thrombus and TIA in patients with AF. Patients with prosthetic aortic or mitral valves, an estimated life expectancy of ⬍3 months, or atrial flutter at the time of enrollment were excluded. After a TEE was performed, 261 of 272 (96%) patients were followed up for a mean of 2.5 years. Follow-up data could not be obtained on 11 patients. The end points included TIA, stroke, peripheral embolism, or death. Left atrial thrombus was detected in 46 (17.6%) of 261 patients, predominately (43/46) isolated to the left atrial appendage. This prevalence was higher than the 13.8% observed in the larger ACUTE study.22 LA SEC was observed in 131 (50%) patients, similar to other studies.21,30 Of the 19 patients who had a TIA, significantly more occurred in patients with (10/46, 21.7%) than without (9/215, 4.2%) an LA thrombus. Combined embolic events occurred more frequently in patients with LA thrombus (15/46, 32.6% vs 28/215, 13%). Patients with an LA thrombus were more likely to be taking warfarin (76% vs 50%) and less likely to be using aspirin (26% vs 44%), compared with those patients without LA thrombus. Those patients with an LA thrombus had greater LA diameters (51.3 mm vs 44.3 mm), higher frequencies of persistent AF (91% vs 67%), lower left ventricular ejection fractions (41% vs 49%), and higher frequencies of LA SEC (72% vs 46%) than the patients without an LA thrombus. The presence of LA SEC and LA thrombus was similar to previously reported studies.21,30 For the entire group, multivariate logistic regression analysis showed congestive heart failure at baseline as the only independent predicator of TIA during follow-up (odds ratio 2.7). With the addition of TEE variables, LA thrombus was the only independent predicator of TIA (odds ratio 7.7). The TIA event rates were 9.2% per year with LA thrombus versus 1.9% without. The embolic events were 13.8% per year and 5.1% per year, respectively. With the exception of a more frequent history of stroke, TIA, or both (10/10 vs 14/36), patients with LA thrombus who had a TIA during follow-up did not differ in frequency of warfarin or aspirin usage in, respectively, congestive heart failure, mitral stenosis, or hypertension. Of note, 46 of 46 with and 201 of 215 without a thrombus were in AF during follow-up. In a subgroup of 203 patients without LA thrombus or mitral stenosis, LA SEC was the only independent predicator of subsequent TIA (odds ratio 4.9). Death rates during follow-up did not differ: 17.5% versus 13.3%. The death rates serve as a reminder that patients with AF have increased mortality.5,6 A rigorous and precise antiembolic strategy was not used in this study. Patients with LA thrombus had TIA develop even though many were identified as taking warfarin. This suggests that either the anticoagulation
Sheahan 583
was subtherapeutic—INR ⬍2.0 — or the therapeutic INR range for those patients with LA thrombus is inadequate. Of the 46 patients with LA thrombus, more than half had a history of stroke or TIA.31 Perhaps a randomized clinical trial comparing standard INR with a higher INR therapeutic range should be considered in patients identified with LA thrombus who are at a higher risk for ischemic stroke. The presence of LA SEC identified patients with a trend for a higher embolic event rate, but the wide confidence intervals associated with LA SEC as a predictor of TIA suggest that SEC may be more of a marker for stasis rather than for embolism. Sinus rhythm does not protect against stroke, as confirmed by the preliminary results from the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial.32 This rhythm versus rate control study did not show a decreased stroke risk in those patients who were maintained in sinus rhythm.32 However, most strokes in both groups occurred in patients not taking warfarin or with a subtherapeutic INR.32 Is it possible that some of the embolic events in this study were noncardioembolic TIA or stroke? Observations on ischemic strokes from the Stroke Prevention in AF I-III clinical studies suggest that most ischemic strokes in AF patients are probably cardioembolic, and these are reduced by adjusted-dose warfarin.33 Aspirin in AF patients appeared to primarily reduce noncardioembolic strokes.33 Implications suggest that aspirin be considered in at-risk patients to prevent nonischemic strokes. The lipid profiles of these patients were not included. Statin therapy has been shown to decrease the risk of ischemic stroke in patients with established coronary artery disease.34,35 Nonarrhythmic primary and secondary risk factor modification also needs to be considered in these older at-risk populations.36,37 At present, there are few options for patients who cannot take warfarin. However, there may be hope on the horizon. The use of the percutaneous left atrial appendage transcatheter occlusion device (PLAATO) to prevent stroke in high-risk patients with AF who are poor candidates for long-term warfarin therapy was shown to be feasible in humans.38 One-month TEE revealed continued stable implant position with smooth atrial-facing surface and no evidence of thrombus.38 The PLAATO approach, if the data are replicated in randomized clinical trials, has the potential to be used in those patients who cannot take warfarin. Stoddard et al31 showed that more than half the patients who had an LA thrombus had a history of stroke or TIA, and many had a subsequent embolic event. These very-high-risk patients with LA thrombus should be considered for a randomized trial comparing the PLAATO approach with conventional warfarin therapy after thrombus resolution.
American Heart Journal April 2003
584 Sheahan
This study reinforces the message that the dance is real, that AF and LA thrombus lead to TIAs. However, those with a negative TEE and AF are still at substantial risk for developing an embolic event—5.1% per year31—similar to the anticipated event rate.39 The current goal for high-risk patients is to carefully monitor and maintain the INR between 2 to 3.15,16,39 With aging or the onset of new cardiac comorbidities, patients who were once considered low risk for the development of thromboembolism transition to a higher risk profile. Now that the dance has been identified, the search to protect the dancer must proceed.
References 1. Yeats WB. Among school children. The Tower. 1928. 2. Benjamin EJ, Levy D, Vaziri EM, et al. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham Heart Study. JAMA 1994;271:840-4. 3. Dorian P, Paquette M, Newman D, et al. Quality of life improves with treatment in the Canadian Trial of Atrial Fibrillation. Am Heart J 2002;143:984-90. 4. Savelieva I, Paquette M, Dorian P, et al. Quality of life in patients with silent atrial fibrillation. Heart 2001;85:216-7. 5. Kannel WB, Abbott RD, Savage DD, et al. Coronary artery disease and atrial fibrillation: The Framingham Study. Am Heart J 1983;106:389-96. 6. Krahn AD, Manfreda J, Tate RB, et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-up Study. Am J Med 1995;98:476-84. 7. Burns A. Observations on formation of polypi of the heart. In: Diseases of the Heart. Edinburgh: Bryce; 1809. 8. Weiss S, Davis D. Rheumatic heart disease. III. Embolic manifestations. Am Heart J 1933;9:45-52. 9. Aberg H. Atrial fibrillation. I. A study of atrial thrombosis and systemic embolism in a necropsy material. Acta Med Scand 1969; 185:373-9. 10. Hinton RC, Kistler JP, Fallon JT, et al. Influence of etiology of atrial fibrillation on incidence of systemic embolism. Am J Cardiology 1977;40:509-13. 11. Lie JT. Atrial fibrillation and left atrial thrombus: an insufferable odd couple. Am Heart J 1988;116:1374-7. 12. Gustafsson C, Blomback M, Britton M, et al. Coagulation factors and the increased risk of stroke in nonvalvular atrial fibrillation. Stroke 1990;21:47-51. 13. Lip GYH. Does atrial fibrillation confer a hypercoagulable state? Lancet 1995;346:1313-4. 14. Mitusch R, Siemens HJ, Garbe M, et al. Detection of a hypercoagulable state in nonvalvular atrial fibrillation and the effect of anticoagulant therapy. Thrombos Haemost 1996:75:219-23. 15. Atrial Fibrillation Investigators. Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Arch Intern Med 1994;154:1449-57. 16. European Atrial Fibrillation Trial Study Group (EAFT). Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke. Lancet 1993;342:1255-62. 17. Fisher CM. Treatment of chronic atrial fibrillation. Lancet 1972;1: 1284. 18. The Stroke Prevention in Atrial Fibrillation Investigators. Predictors
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20.
21.
22.
23.
24.
25.
26.
27.
28.
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30.
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32.
33.
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