ATRIAL FIBRILLATION
Prognostic Significance of Left Atrial Appendage ‘‘Sludge’’ in Patients with Atrial Fibrillation: A New Transesophageal Echocardiographic Thromboembolic Risk Factor Boris S. Lowe, MD, Kenya Kusunose, MD, PhD, Hirohiko Motoki, MD, PhD, Brandon Varr, MD, Kevin Shrestha, MD, Christine Whitman, RN, W. H. Wilson Tang, MD, James D. Thomas, MD, and Allan L. Klein, MD, Cleveland, Ohio
Background: When stratifying thromboembolic risk to patients with atrial fibrillation (AF), left atrial appendage (LAA) thrombus is currently the only echocardiographic index that absolutely contraindicates cardioversion. The aim of this study was to identify the predictors of LAA ‘‘sludge’’ and its impact on subsequent thromboembolism and survival in patients with AF. Methods: A total of 340 patients (mean age, 66 6 12 years; 75% men) who underwent transesophageal echocardiography to exclude LAA thrombus before electrical cardioversion or radiofrequency pulmonary vein isolation) for AF were retrospectively studied. LAA sludge was defined as a dynamic, viscid, layered echodensity without a discrete mass, visualized throughout the cardiac cycle. Follow-up was obtained after a mean of 6.7 6 3.7 years, and patients were analyzed according to LAA thrombus (n = 62 [18%]), sludge (n = 47 [14%]), or spontaneous echocardiographic contrast (n = 84 [25%]). Patients without these transesophageal echocardiographic characteristics served as controls (n = 147 [43%]). Results: LAA sludge was independently predicted by enlarged left atrial area (odds ratio, 4.54; 95% confidence interval [CI], 2.38–8.67; P < .001), reduced LAA emptying velocity (odds ratio, 12.7; 95% CI, 6.11–26.44; P < .001), and reduced left ventricular ejection fraction (odds ratio, 2.11; 95% CI, 1.03–4.32; P < .001). Thromboembolic event and all-cause mortality rates in patients with sludge were 23% and 57%, respectively. Multiple logistic regression analyses identified the presence of LAA sludge to be independently associated with thromboembolic complications (adjusted hazard ratio, 3.43; 95% CI, 1.42–8.28; P = .006) and allcause mortality (adjusted hazard ratio, 2.02; 95% CI, 1.22–3.36; P = .007). Conclusion: Sludge within the LAA is independently associated with subsequent thromboembolic events and all-cause mortality in patients with AF. (J Am Soc Echocardiogr 2014;27:1176-83.) Keywords: Atrial fibrillation, Cardioversion, Echocardiography, Stroke, Mortality
Among the clinical and echocardiographic indices used to stratify thromboembolic risk to patients with atrial fibrillation (AF), left atrial (LA) appendage (LAA) thrombus is a powerful predictor of increased risk and stands as the only absolute contraindication to cardioversion.1 Spontaneous echocardiographic contrast (SEC) is associated with a high incidence of thrombus formation and thromboembolic events,2-7 but there is no consensus that cardioversion is contraindicated in
patients without coexistent LA or LAA thrombus identified. Current AF management guidelines do not recognize ‘‘sludge’’ within the LAA as an entity identified by transesophageal echocardiography (TEE). Although sludge may be regarded as a precursor to thrombus, the long-term fate of these patients has not been reported. In this study, we investigated the predictors of LAA sludge without thrombus and its impact on subsequent thromboembolism and survival in patients with AF.
From the Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
METHODS
Drs Lowe and Kusunose contributed equally to this work.
Patients The study was approved by the institutional review board. The source population for this retrospective case-control series was identified from the Cleveland Clinic Adult Echocardiography Laboratory Database between 1996 and 2005. During the study period, we identified 491 consecutive patients with electrocardiographically
Reprint requests: Allan L. Klein, MD, Cleveland Clinic, Heart and Vascular Institute, 9500 Euclid Avenue, Desk J1-5, Cleveland, OH 44195 (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2014 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2014.08.016
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Lowe et al 1177
Journal of the American Society of Echocardiography Volume 27 Number 11
Abbreviations
AF = Atrial fibrillation CI = Confidence interval HR = Hazard ratio INR = International normalized ratio LA = Left atrial LAA = Left atrial appendage LVEF = Left ventricular ejection fraction
PVI = Pulmonary vein isolation SEC = Spontaneous echocardiographic contrast
TEE = Transesophageal echocardiography
documented permanent or paroxysmal AF who were referred for TEE to exclude thrombus within the LAA. Patients with valvular AF (n = 17) or prosthetic valves (n = 42) were excluded because of the established association with AF and thromboembolism. We also excluded patients who did not undergo transthoracic echocardiography within 1 month of index TEE (n = 76) and those without Social Security numbers (n = 16). A total of 340 patients were included for the final analysis. The baseline clinical and echocardiographic characteristics of the 340 study subjects are described in Table 1 and Table 2, respectively.
Echocardiographic Studies An Acuson Sequoia (Siemens Medical Solutions USA, Inc, Mountain View, CA) or ATL 5000 (Philips Medical Systems, Andover, MA) echocardiographic system and a multiplane 5- to 7.5-MHz transducer were used for dedicated TEE to visualize the left atrium and LAA from multiple planes. Digital cine loops and/or standard VHS tapes of all echocardiographic studies were evaluated offline (ProSolv Cardiovascular Analyzer 3.5; Problem Solving Concepts, Indianapolis, IN) in consensus by two experienced readers (B.S.L., A.L.K.) blinded to the clinical data. SEC was recognized as dynamic, swirling, smokelike echoes within the LAA cavity.8 LAA sludge was defined as an intracavitary echodensity with viscid gelatinous qualities giving the impression of impending precipitation, but without a discrete organized mass, continuously seen throughout the cardiac cycle.9 Sludge appears more dense and layered than severe SEC (Figure 1, Videos 1–4; available at www. onlinejase.com). LAA thrombus was defined from multiple imaging planes as a well-circumscribed, solid echodensity acoustically distinct from the underlying endocardium and pectinate muscles that was less heterogeneous and dynamic than sludge.10,11 Patients were analyzed according to the appearance within the left atrium and LAA on the index TEE: thrombus (n = 62 [18%]), sludge (n = 47 [14%]), and SEC (n = 84 [25%]). The control group consisted of 147 patients (43%) without LAA thrombus, sludge, or SEC. Patients with coexistent appearances were assigned to the higher thrombogenic spectrum group for analysis (thrombus > sludge > SEC > none). LAA emptying velocities were evaluated during TEE using pulsedwave Doppler with a sample volume placed 1 cm into the LAA at transducer phased-array angles of 45 to 120 . Low LAA velocities were defined as
Prognostic Significance of Left Atrial Appendage ‘‘Sludge’’ in Patients with Atrial Fibrillation: A New Transesophageal Echocardiographic Thromboembolic Risk Factor Boris S. Lowe, MD, Kenya Kusunose, MD, PhD, Hirohiko Motoki, MD, PhD, Brandon Varr, MD, Kevin Shrestha, MD, Christine Whitman, RN, W. H. Wilson Tang, MD, James D. Thomas, MD, and Allan L. Klein, MD, Cleveland, Ohio
Background: When stratifying thromboembolic risk to patients with atrial fibrillation (AF), left atrial appendage (LAA) thrombus is currently the only echocardiographic index that absolutely contraindicates cardioversion. The aim of this study was to identify the predictors of LAA ‘‘sludge’’ and its impact on subsequent thromboembolism and survival in patients with AF. Methods: A total of 340 patients (mean age, 66 6 12 years; 75% men) who underwent transesophageal echocardiography to exclude LAA thrombus before electrical cardioversion or radiofrequency pulmonary vein isolation) for AF were retrospectively studied. LAA sludge was defined as a dynamic, viscid, layered echodensity without a discrete mass, visualized throughout the cardiac cycle. Follow-up was obtained after a mean of 6.7 6 3.7 years, and patients were analyzed according to LAA thrombus (n = 62 [18%]), sludge (n = 47 [14%]), or spontaneous echocardiographic contrast (n = 84 [25%]). Patients without these transesophageal echocardiographic characteristics served as controls (n = 147 [43%]). Results: LAA sludge was independently predicted by enlarged left atrial area (odds ratio, 4.54; 95% confidence interval [CI], 2.38–8.67; P < .001), reduced LAA emptying velocity (odds ratio, 12.7; 95% CI, 6.11–26.44; P < .001), and reduced left ventricular ejection fraction (odds ratio, 2.11; 95% CI, 1.03–4.32; P < .001). Thromboembolic event and all-cause mortality rates in patients with sludge were 23% and 57%, respectively. Multiple logistic regression analyses identified the presence of LAA sludge to be independently associated with thromboembolic complications (adjusted hazard ratio, 3.43; 95% CI, 1.42–8.28; P = .006) and allcause mortality (adjusted hazard ratio, 2.02; 95% CI, 1.22–3.36; P = .007). Conclusion: Sludge within the LAA is independently associated with subsequent thromboembolic events and all-cause mortality in patients with AF. (J Am Soc Echocardiogr 2014;27:1176-83.) Keywords: Atrial fibrillation, Cardioversion, Echocardiography, Stroke, Mortality
Among the clinical and echocardiographic indices used to stratify thromboembolic risk to patients with atrial fibrillation (AF), left atrial (LA) appendage (LAA) thrombus is a powerful predictor of increased risk and stands as the only absolute contraindication to cardioversion.1 Spontaneous echocardiographic contrast (SEC) is associated with a high incidence of thrombus formation and thromboembolic events,2-7 but there is no consensus that cardioversion is contraindicated in
patients without coexistent LA or LAA thrombus identified. Current AF management guidelines do not recognize ‘‘sludge’’ within the LAA as an entity identified by transesophageal echocardiography (TEE). Although sludge may be regarded as a precursor to thrombus, the long-term fate of these patients has not been reported. In this study, we investigated the predictors of LAA sludge without thrombus and its impact on subsequent thromboembolism and survival in patients with AF.
From the Section of Cardiovascular Imaging, Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
METHODS
Drs Lowe and Kusunose contributed equally to this work.
Patients The study was approved by the institutional review board. The source population for this retrospective case-control series was identified from the Cleveland Clinic Adult Echocardiography Laboratory Database between 1996 and 2005. During the study period, we identified 491 consecutive patients with electrocardiographically
Reprint requests: Allan L. Klein, MD, Cleveland Clinic, Heart and Vascular Institute, 9500 Euclid Avenue, Desk J1-5, Cleveland, OH 44195 (E-mail: [email protected]). 0894-7317/$36.00 Copyright 2014 by the American Society of Echocardiography. http://dx.doi.org/10.1016/j.echo.2014.08.016
1176
Lowe et al 1177
Journal of the American Society of Echocardiography Volume 27 Number 11
Abbreviations
AF = Atrial fibrillation CI = Confidence interval HR = Hazard ratio INR = International normalized ratio LA = Left atrial LAA = Left atrial appendage LVEF = Left ventricular ejection fraction
PVI = Pulmonary vein isolation SEC = Spontaneous echocardiographic contrast
TEE = Transesophageal echocardiography
documented permanent or paroxysmal AF who were referred for TEE to exclude thrombus within the LAA. Patients with valvular AF (n = 17) or prosthetic valves (n = 42) were excluded because of the established association with AF and thromboembolism. We also excluded patients who did not undergo transthoracic echocardiography within 1 month of index TEE (n = 76) and those without Social Security numbers (n = 16). A total of 340 patients were included for the final analysis. The baseline clinical and echocardiographic characteristics of the 340 study subjects are described in Table 1 and Table 2, respectively.
Echocardiographic Studies An Acuson Sequoia (Siemens Medical Solutions USA, Inc, Mountain View, CA) or ATL 5000 (Philips Medical Systems, Andover, MA) echocardiographic system and a multiplane 5- to 7.5-MHz transducer were used for dedicated TEE to visualize the left atrium and LAA from multiple planes. Digital cine loops and/or standard VHS tapes of all echocardiographic studies were evaluated offline (ProSolv Cardiovascular Analyzer 3.5; Problem Solving Concepts, Indianapolis, IN) in consensus by two experienced readers (B.S.L., A.L.K.) blinded to the clinical data. SEC was recognized as dynamic, swirling, smokelike echoes within the LAA cavity.8 LAA sludge was defined as an intracavitary echodensity with viscid gelatinous qualities giving the impression of impending precipitation, but without a discrete organized mass, continuously seen throughout the cardiac cycle.9 Sludge appears more dense and layered than severe SEC (Figure 1, Videos 1–4; available at www. onlinejase.com). LAA thrombus was defined from multiple imaging planes as a well-circumscribed, solid echodensity acoustically distinct from the underlying endocardium and pectinate muscles that was less heterogeneous and dynamic than sludge.10,11 Patients were analyzed according to the appearance within the left atrium and LAA on the index TEE: thrombus (n = 62 [18%]), sludge (n = 47 [14%]), and SEC (n = 84 [25%]). The control group consisted of 147 patients (43%) without LAA thrombus, sludge, or SEC. Patients with coexistent appearances were assigned to the higher thrombogenic spectrum group for analysis (thrombus > sludge > SEC > none). LAA emptying velocities were evaluated during TEE using pulsedwave Doppler with a sample volume placed 1 cm into the LAA at transducer phased-array angles of 45 to 120 . Low LAA velocities were defined as
