REVIEW URRENT C OPINION
Left atrial volume and function in patients with atrial fibrillation Darryl P. Leong and Hisham Dokainish
Purpose of review This review of emerging approaches to left atrial imaging in atrial fibrillation is relevant because there has been considerable recent development in the noninvasive characterization of left atrial structure and function. Concurrently, the identification and treatment of atrial fibrillation and the prevention of thromboembolism are evolving. Thus, it is timely to summarize how the advances in these two areas might be synergistic in the treatment of atrial fibrillation. Recent findings This article will summarize recent developments in left atrial imaging that play a role in patients with atrial fibrillation, with particular emphasis on echocardiography, and with reference made to important advances in cardiac computed tomography and cardiac magnetic resonance. The evidence that these modalities can predict who will develop atrial fibrillation, who will achieve sustained sinus rhythm after cardioversion or catheter ablation, and who will have thromboembolic risk will be reviewed. Summary Although existing evidence is promising, the clinical role of cardiac imaging to predict atrial fibrillation occurrence, atrial fibrillation recurrence after treatment, and thromboembolism from atrial fibrillation remains to be confirmed in large-scale studies and clinical trials. Keywords atrial fibrillation, echocardiography, imaging, thromboembolism
INTRODUCTION Atrial fibrillation is common and is expected to grow in prevalence due to ageing populations with a greater burden of chronic cardiovascular disease. Advances in cardiac imaging techniques, permitting detailed characterization of atrial morphology and function, can provide insight into the natural history of atrial fibrillation and enhance the prediction of clinical outcomes and response to treatments. The purpose of this review is to summarize recent developments in left atrial imaging that play a role in individualized patient care, with particular emphasis on echocardiography, and with reference made to important advances in cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR).
LEFT ATRIAL REMODELING AND CHANGES IN LEFT ATRIAL FUNCTION IN ATRIAL FIBRILLATION Atrial fibrillation is characterized by a spectrum of pathological changes that may result from ageing and that may be accelerated by disease processes, such as hypertension, ischemic heart disease,
valvular heart disease, and tachycardia. Current understanding of the relationship between the pathophysiologic determinants of atrial fibrillation, ultrastructural and histological changes to the left atrium, and macroscopic left atrial remodeling are largely inferred from animal models. These models suggest that atrial fibrillation may occur on a pathologic continuum beginning with myocytolysis [1] and myocyte dedifferentiation, and culminating with atrial fibrosis [2]. These pathologic processes are associated with both left atrial dilatation and impairment of left atrial mechanical function. Indeed, experimental evidence suggests that left atrial dilatation and mechanical Department of Medicine, Division of Cardiology, McMaster University Hamilton, ON, Canada Correspondence to Hisham Dokainish, MD, FRCPC, FASE, FACC, Associate Professor of Medicine, McMaster University, Director of Echocardiography, Hamilton Health Sciences, 237 Barton St E., CVSRI #C3 111, Hamilton, ON L8L 2X2, Canada. Tel. +1 905 527 4322 ext. 40327; e-mail: [email protected] Curr Opin Cardiol 2014, 29:437–444 DOI:10.1097/HCO.0000000000000088
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KEY POINTS • Left atrial remodeling (dilation) and impaired left atrial function – by 2D and strain echocardiography – is an important predictor of the development of atrial fibrillation in patients at risk. • Left atrial fibrosis – as represented by impaired echocardiographic left atrial strain and delayed enhancement on CMR – is inversely associated with the ability to restore sinus rhythm in patients with atrial fibrillation. • Increasing left atrial volume, decreasing left atrial strain, and different and more complex left atrial appendage morphologies, by echocardiography, have been associated with an increasing risk of stroke.
dysfunction may predispose to atrial fibrillation [3] (as well as resulting from it), thus creating a vicious cycle that acts to perpetuate atrial fibrillation. Moreover, in patients with atrial fibrillation, there is a positive relationship between left atrial size and atrial fibrillation burden, and a negative relationship between left atrial function and atrial fibrillation burden [4]. Accurate evaluation of left atrial volume and function is important in the characterization of individuals with or at risk of atrial fibrillation and in the evaluation of strategies to treat or prevent atrial fibrillation. Recent advances in echocardiographic approaches to assess left atrial size and
function are important in this regard. Three-dimensional (3D) echocardiography has shown close correlation and minimal bias compared with CMR for the measurement of LA volume [5] and is superior to two-dimensional (2D) echocardiography because image foreshortening can be overcome [6] (Fig. 1). Speckle-tracking approaches to assess left atrial myocardial deformation (strain) and rate of deformation (strain rate) reflect the extent of left atrial fibrosis as measured by late-gadolinium enhancement CMR [7]. Three-dimensional echocardiography and speckle-tracking analysis of left atrial function prominently feature in the potential clinical role of assessing left atrial size and function in the recent literature.
LEFT ATRIAL STRUCTURE AND FUNCTION TO PREDICT OCCURRENCE OF ATRIAL FIBRILLATION The prediction of atrial fibrillation in patients with sinus rhythm is desirable because it may provide an opportunity to prevent systemic thromboembolism – a major complication of atrial fibrillation – which is often the first clinical manifestation of atrial fibrillation [8]. Left atrial size has long been recognized as a predictor of incident atrial fibrillation. Among 486 patients with intermittent atrial fibrillation, Flaker et al. [9] showed that left atrial diameter was associated with atrial fibrillation recurrence. In a study of 1655 patients without known atrial fibrillation, a 30% larger left atrial volume was associated with a 43% increased risk of incident
FIGURE 1. Left atrial volume by three-dimensional transthoracic echocardiography. The panel of four images on the left illustrate orthogonal apical views of the left atrium. The three images on the right demonstrate corresponding short-axis views of the left atrium at the levels indicated by the dashed lines. The left atrial volume by three-dimensional echocardiography is calculated at 44.5 ml, which is within normal limits. 438
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Left atrial volume and function in patients with atrial fibrillation Leong and Dokainish
atrial fibrillation [10]. These findings have been mirrored by a population-based CCT study of 3905 patients that showed that left atrial area is a strong predictor of incident atrial fibrillation [11]. Although left atrial size can be evaluated echocardiographically by linear dimension, it is recommended that left atrial size be assessed by volume measurement, due to the inaccuracy of linear dimension [12]. Moreover, despite evidence that measurement of left atrial size provides incremental predictive value to clinical factors for the occurrence of atrial fibrillation, it is unclear whether and how this could be translated to clinical practice [13]. Although one can identify individuals who are more likely to have or to develop atrial fibrillation, it is unclear how to monitor for atrial fibrillation. While 3D echocardiography represents a major advance in the echocardiographic measurement of cardiac volumes, it remains to be seen whether this approach to the quantification of left atrial volume will confer an advantage over 2D measurements in risk stratification for the development of atrial fibrillation. Left atrial mechanical dysfunction is an important part of the pathophysiology of atrial fibrillation. However, it can be challenging to noninvasively image the left atrium in the three phases of mechanical function: reservoir, conduit, and contractile (Fig. 2). Consequently, no consensus exists as to the ideal imaging approach to assess left atrial function. Left atrial strain and strain rate, which are measures of left atrial deformation and deformation rate, respectively, hold particular promise. Left atrial strain and strain rate can be measured by either tissue Doppler or speckle-tracking techniques (Figs 3 and 4). Tissue Doppler approaches are more technically demanding and time consuming, whereas speckle-tracking techniques are somewhat easier. In a study of controls and patients with atrial fibrillation using tissue Doppler strain rate, Inaba et al. [14] found significant differences between groups in reservoir and conduit peaks, but could not demonstrate a difference in the atrial contractile peak. In 63 patients with sinus rhythm and 37 patients with atrial fibrillation or atrial flutter, Leong et al. [15] reported that reservoir and atrial contractile strain rate as well as reservoir strain – whether by tissue Doppler or speckle-tracking approaches – differed between the groups, but that speckle-tracking approaches had superior discriminatory ability for the presence of moderate–severe spontaneous echocardiographic contrast on transesophageal echocardiography (TEE). Kojima et al. [16], using velocity vector imaging, found that not only were left atrial volumes larger in patients
with paroxysmal atrial fibrillation compared with those with no history of atrial fibrillation, but also left atrial function in sinus rhythm was worse in the former group even after adjustment for left atrial volume. In a study of individuals more than 50 years of age, left atrial speckle-tracking strain was the best predictor of a composite of incident cardiovascular events, including atrial fibrillation, which developed in 16 (51%) of the cohort after 3.1 1.4 years of follow-up [17]. Among 580 patients without known atrial fibrillation or mitral valve disease, Hirose et al. [18] found that left atrial speckle-tracking strain was the strongest overall predictor of incident atrial fibrillation; left atrial deformation 37% or less exhibited a positive predictive value (95% confidence interval) of 19% (16–22%) and a negative predictive value (95% confidence interval) of 99% (98–100%). In 101 patients with mild mitral stenosis in sinus rhythm and 70 healthy controls, Ancona et al. [19] reported that speckle-tracking reservoir left atrial strain was the best predictor of incident atrial fibrillation, although the optimal discriminatory threshold in this patient population was 17.4%, which differs from the 37% threshold reported by Hirose et al. [18]. In summary, evaluation of left atrial size can help to identify individuals who will develop atrial fibrillation. There is also growing evidence that echocardiographic measurement of left atrial deformation and function may improve risk prediction of incident atrial fibrillation; however, whether left atrial evaluation should be implemented in clinical practice and should prompt strategies to lower thromboembolic risk remain unclear.
LA volume
LAmax
LApreA
LAmin Reservoir function = 100.(LAmax – LAmin)/LAmin Conduit function = 100.(LAmax – LApreA)/LAmax Contractile function = 100.(LApreA – LAmin)/LApreA
FIGURE 2. Phases of left atrial function. LAmax, maximum left atrial volume; LAmin, minimum left atrial volume; LApreA, left atrial volume at the onset of the A wave. Reproduced with permission from [20].
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(a)
(b) RSr
ASr CSr
FIGURE 3. Left atrial strain (a) and strain rate (b) by speckle-tracking echocardiography. The arrow indicates the peak of the white curve that represents averaged segmental strain scores from the left atrium. ASr, atrial contractile strain rate; CSr, conduit strain rate; RSr, reservoir strain rate. Reproduced by permission from Oxford University Press on behalf of the European Society of Cardiology from [15].
LEFT ATRIAL VOLUME AND FUNCTION TO PREDICT SUCCESS OF CARDIOVERSION OF ATRIAL FIBRILLATION Cardioversion of atrial fibrillation may be recommended for selected individuals as part of a longterm strategy of rhythm control [21]. For many, cardioversion of atrial fibrillation is unsuccessful 440
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or atrial fibrillation recurs within a short period of time; thus, a-priori identification of such patients may be useful. In a multicenter European registry, Pisters et al. [22] found that smaller left atrial diameter was independently associated with the long-term maintenance of sinus rhythm after electrical Volume 29 • Number 5 • September 2014
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Left atrial volume and function in patients with atrial fibrillation Leong and Dokainish
(a)
RSr (b)
CSr
ASr
FIGURE 4. Left atrial strain (a) and strain rate (b) by tissue Doppler imaging. The arrow indicates peak left atrial strain. ASr, atrial contractile strain rate; CSr, conduit strain rate; RSr, reservoir strain rate. Reproduced by permission from Oxford University Press on behalf of the European Society of Cardiology from [15].
cardioversion. Di Salvo et al. [23] studied 65 consecutive patients undergoing cardioversion for lone atrial fibrillation, finding that tissue Doppler left atrial strain and strain rate were independent predictors of the maintenance of sinus rhythm over the subsequent 9 months. In a study of patients undergoing pharmacologic cardioversion of atrial fibrillation with intravenous
flecainide, Limantoro et al. [24] found that both the atrial fibrillation cycle length and the atrial fibrillation tissue velocity, by color-coded tissue velocity imaging of the lateral left atrial wall, were reasonable discriminators of the immediate success of pharmacologic cardioversion, with areas under the receiver operating characteristic curve of 0.78 and 0.79, respectively. The clinical
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usefulness of this approach is uncertain, however, because it requires easy access to echocardiography and expertise in performing the required measurements (both of which may be challenging in the emergency department setting) and was only feasible in 55% of patients studied.
LEFT ATRIAL STRUCTURE AND FUNCTION TO PREDICT SUCCESS OF CATHETER ABLATION OF ATRIAL FIBRILLATION Atrial fibrillation ablation may be recommended as a therapeutic approach to symptom control for patients with paroxysmal atrial fibrillation [25]; therefore, imaging predictors of patients who are more likely to derive benefit would be of value. In a study of consecutive patients undergoing atrial fibrillation catheter ablation, Marsan et al. [26] found that preablation left atrial volume index by 3D transthoracic echocardiography was significantly larger in patients who developed atrial fibrillation recurrence (31 8 ml/m2) compared with those who maintained sinus rhythm (26 8 ml/m2; P < 0.05) during 7.9 months’ follow-up. Among 73 patients undergoing atrial fibrillation ablation, Helms et al. [27] found that left atrial volume more than 135 ml, by CCT, had a sensitivity of 36% and specificity of 96% for atrial fibrillation recurrence over 12 months’ follow-up. In a study of patients undergoing a first atrial fibrillation ablation, Marrouche et al. [28 ] demonstrated, using late gadolinium enhancement CMR, that there was a significant relationship between noninvasively quantified left atrial fibrosis and atrial fibrillation recurrence. Schneider et al. [29] measured left atrial dimensions and tissue Doppler strain and strain rate before and 24 h after atrial fibrillation ablation, finding that no preablation clinical or echocardiographic characteristic distinguished patients who would maintain sinus rhythm at 3 months [29]. These findings contrast with those of Hammerstingl et al. [30], who reported that a global left atrial strain threshold of 10.79% in the apical four-chamber view had a positive predictive value of 78.8% and a negative predictive value of 93.9% for the recurrence of atrial fibrillation following catheter ablation. Prior to atrial fibrillation ablation, echocardiography and (for pulmonary vein characterization) either CCT or CMR are often performed. When different estimates of left atrial volume are available, 2D measurements underestimate left atrial volume compared with 3D measurements [31]. Additionally, superior signal-to-noise ratio of CCT or CMR compared with echocardiography may make these more reliable modalities when available. However, further studies of &&
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3D echocardiographic left atrial volume compared with MRI or computed tomography are warranted.
LEFT ATRIAL VOLUME AND FUNCTION TO PREDICT STROKE RISK FROM ATRIAL FIBRILLATION In patients with atrial fibrillation, the benefits of anticoagulation for the prevention of thromboembolism must be weighed against the risk of bleeding. While clinical tools can help predict an individual’s risk of stroke, their discriminatory ability is limited [32]. By detailed left atrial characterization, imaging techniques may further refine stroke risk stratification for patients with atrial fibrillation. In a study of patients with atrial fibrillation, stroke/transient ischemic attack, and CHADS2 scores 1 or lower, and controls with atrial fibrillation but no history of cerebrovascular disease, left atrial speckle-tracking strain was independently associated with stroke [33]. These findings suggest that, in individuals with atrial fibrillation who are thought to have a low stroke risk on clinical grounds, speckletracking strain may help reclassify some individuals into a higher risk group. Indeed, even in a group of patients with permanent atrial fibrillation and higher stroke risk than that seen in the previous study, Shih et al. [34] found that left atrial speckletracking strain and strain rate were independently associated with stroke risk. There is some evidence of an association between left atrial spontaneous echocardiographic contrast/ appendage emptying velocity measured by TEE and left atrial thromboembolism [35]. In a randomized, controlledtrial,randomizing patientswithatrialfibrillation and an indication for anticoagulation to a vitamin K antagonist or aspirin on the basis of TEE findings of left atrial blood stasis or complex aortic plaque [36], aspirin was found to be noninferior to vitamin K antagonist with respect to the primary endpoint of stroke, major bleeding, and peripheral embolism. The left atrial appendage, an important putative source of thromboembolism, has heterogeneous morphology. Di Biase et al. [37] categorized the left atrial appendage into one of four morphologic patterns on the basis of CCT or CMR, performed on 932 patients with atrial fibrillation planned for ablation, finding that stroke risk varied with left atrial appendage type: a ‘Chicken wing’ appendage, typified by a bend in the proximal or middle part of the dominant appendage lobe, was associated with a lower risk of stroke, and a ‘Cauliflower’ appendage, with a more lobulated, complex morphology, was associated with a higher risk of stroke. Using TEE in patients with atrial fibrillation, Yamamoto et al. [38 ] examined the relationship between the number of left atrial appendage &
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lobes and the presence of left atrial appendage thrombus, finding that 94% of patients with left atrial appendage thrombus had at least three left atrial appendage lobes. While the left atrial appendage has been thought to be important in thromboembolism for some time, the technology to move beyond left atrial size to a more refined characterization of chamber morphology, with the goal of thromboembolic risk stratification, has only recently been explored.
CONCLUSION Left atrial volume assessment is important in the prediction of atrial fibrillation occurrence and recurrence after rhythm-control therapies. When available, 3D imaging approaches to left atrial characterization permit more accurate measurement of left atrial volume. Recently, there has been particular growth in research into the role of speckle-tracking strain approaches, in particular, to evaluate left atrial function, and how this evaluation can predict the incidence of atrial fibrillation and potentially guide the treatment of atrial fibrillation; yet, there are significant obstacles to the widespread clinical uptake of left atrial speckle-tracking imaging, such as a paucity of outcomes research, and it remains uncertain whether the use of speckle-tracking should alter clinical practice. Also, multicenter studies, which are important to demonstrate the widespread utility of speckle-tracking outside research institutions, are lacking. Little information is available on intervendor comparability; however, CMR and CCT to assess left atrial structure and function show significant promise in patients with atrial fibrillation and are being increasingly used to understand the optimal risk stratification and management of this important and growing patient population. Acknowledgements None. Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the period of review, have been highlighted as: & of special interest && of outstanding interest 1. Ausma J, van der Velden HM, Lenders MH, et al. Reverse structural and gap-junctional remodeling after prolonged atrial fibrillation in the goat. Circulation 2003; 107:2051–2058. 2. Burstein B, Nattel S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol 2008; 51:802–809.
3. Schotten U, de Haan S, Neuberger HR, et al. Loss of atrial contractility is primary cause of atrial dilatation during first days of atrial fibrillation. Am J Physiol Heart Circ Physiol 2004; 287:H2324–H2331. 4. Gupta DK, Shah AM, Giugliano RP, et al. Left atrial structure and function in atrial fibrillation. ENGAGE AF-TIMI 48. Eur Heart J 2013. [Epub ahead of print] 5. Mor-Avi V, Yodwut C, Jenkins C, et al. Real-time 3D echocardiographic quantification of left atrial volume: multicenter study for validation with CMR. JACC Cardiovasc Imag 2012; 5:769–777. 6. Iwataki M, Takeuchi M, Otani K, et al. Measurement of left atrial volume from transthoracic three-dimensional echocardiographic datasets using the biplane Simpson’s technique. J Am Soc Echocardiogr 2012; 25:1319– 1326. 7. Kuppahally SS, Akoum N, Burgon NS, et al. Left atrial strain and strain rate in patients with paroxysmal and persistent atrial fibrillation: relationship to left atrial structural remodeling detected by delayed-enhancement MRI. Circ Cardiovasc Imag 2010; 3:231–239. 8. Lin HJ, Wolf PA, Benjamin EJ, et al. Newly diagnosed atrial fibrillation and acute stroke. The Framingham study. Stroke 1995; 26:1527– 1530. 9. Flaker GC, Fletcher KA, Rothbart RM, et al. Clinical and echocardiographic features of intermittent atrial fibrillation that predict recurrent atrial fibrillation. Stroke Prevention in Atrial Fibrillation (SPAF) investigators. Am J Cardiol 1995; 76:355–358. 10. Tsang TS, Barnes ME, Bailey KR, et al. Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women. Mayo Clin Proc 2001; 76:467–475. 11. Mahabadi AA, Lehmann N, Kalsch H, et al. Association of epicardial adipose tissue and left atrial size on noncontrast CT with atrial fibrillation: the Heinz Nixdorf recall study. Eur Heart J Cardiovasc Imag 2014. [Epub ahead of print] 12. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005; 18:1440–1463. 13. Quinn FR, Gladstone D. Screening for undiagnosed atrial fibrillation in the community. Curr Opin Cardiol 2014; 29:28–35. 14. Inaba Y, Yuda S, Kobayashi N, et al. Strain rate imaging for noninvasive functional quantification of the left atrium: Comparative studies in controls and patients with atrial fibrillation. J Am Soc Echocardiogr 2005; 18:729–736. 15. Leong DP, Penhall A, Perry R, et al. Speckle-tracking strain of the left atrium: a transoesophageal echocardiographic validation study. Eur Heart J Cardiovasc Imag 2013; 14:898–905. 16. Kojima T, Kawasaki M, Tanaka R, et al. Left atrial global and regional function in patients with paroxysmal atrial fibrillation has already been impaired before enlargement of left atrium: velocity vector imaging echocardiography study. Eur Heart J Cardiovasc Imag 2012; 13:227–234. 17. Cameli M, Lisi M, Focardi M, et al. Left atrial deformation analysis by speckle tracking echocardiography for prediction of cardiovascular outcomes. Am J Cardiol 2012; 110:264–269. 18. Hirose T, Kawasaki M, Tanaka R, et al. Left atrial function assessed by speckle tracking echocardiography as a predictor of new-onset nonvalvular atrial fibrillation: results from a prospective study in 580 adults. Eur Heart J Cardiovasc Imag 2012; 13:243–250. 19. Ancona R, Comenale Pinto S. Two-dimensional atrial systolic strain imaging predicts atrial fibrillation at 4-year follow-up in asymptomatic rheumatic mitral stenosis. J Am Soc Echocardiogr 2013; 26:270–277. 20. Leong DP, Delgado V, Bax JJ. Imaging for atrial fibrillation. Curr Probl Cardiol 2012; 37:7–33. 21. Wann LS, Curtis AB, Ellenbogen KA, et al. Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/ AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127:1916–1926. 22. Pisters R, Nieuwlaat R, Prins MH, et al. Clinical correlates of immediate success and outcome at 1-year follow-up of real-world cardioversion of atrial fibrillation: the Euro Heart Survey. Europace 2012; 14:666–674. 23. Di Salvo G, Caso P, Lo Piccolo R, et al. Atrial myocardial deformation properties predict maintenance of sinus rhythm after external cardioversion of recent-onset lone atrial fibrillation: a color Doppler myocardial imaging and transthoracic and transesophageal echocardiographic study. Circulation 2005; 112:387–395. 24. Limantoro I, De Vos CB, Delhaas T, et al. Tissue velocity imaging of the left atrium predicts response to flecainide in patients with acute atrial fibrillation. Heart Rhythm 2014; 11:478–484. 25. Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33:2719–2747.
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Imaging and echocardiography 26. Marsan NA, Tops LF, Holman ER, et al. Comparison of left atrial volumes and function by real-time three-dimensional echocardiography in patients having catheter ablation for atrial fibrillation with persistence of sinus rhythm versus recurrent atrial fibrillation three months later. Am J Cardiol 2008; 102:847–853. 27. Helms AS, West JJ, Patel A, et al. Relation of left atrial volume from threedimensional computed tomography to atrial fibrillation recurrence following ablation. Am J Cardiol 2009; 103:989–993. 28. Marrouche NF, Wilber D, Hindricks G, et al. Association of atrial tissue && fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: The DECAAF study. JAMA 2014; 311:498–506. This multicenter study demonstrated that left atrial fibrosis as quantified by late gadolinium cardiac magnetic resonance could predict success of catheter ablation for atrial fibrillation, raising the possibility that this technique could be applied in clinical practice in centers without specific expertise in atrial late gadolinium enhancement cardiac magnetic resonance. 29. Schneider C, Malisius R, Krause K, et al. Strain rate imaging for functional quantification of the left atrium: atrial deformation predicts the maintenance of sinus rhythm after catheter ablation of atrial fibrillation. Eur Heart J 2008; 29:1397–1409. 30. Hammerstingl C, Schwekendiek M, Momcilovic D, et al. Left atrial deformation imaging with ultrasound based two-dimensional speckletracking predicts the rate of recurrence of paroxysmal and persistent atrial fibrillation after successful ablation procedures. J Cardiovasc Electrophysiol 2012; 23:247–255. 31. Tops LF, van der Wall EE, Schalij MJ, Bax JJ. Multi-modality imaging to assess left atrial size, anatomy and function. Heart 2007; 93:1461–1470.
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32. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182678 patients with atrial fibrillation: the Swedish atrial fibrillation cohort study. Eur Heart J 2012; 33:1500–1510. 33. Azemi T, Rabdiya VM, Ayirala SR, et al. Left atrial strain is reduced in patients with atrial fibrillation, stroke or TIA, and low risk CHADS(2) scores. J Am Soc Echocardiogr 2012; 25:1327–1332. 34. Shih JY, Tsai WC, Huang YY, et al. Association of decreased left atrial strain and strain rate with stroke in chronic atrial fibrillation. J Am Soc Echocardiogr 2011; 24:513–519. 35. Fatkin D, Kelly RP, Feneley MP. Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast and thromboembolic risk in vivo. J Am Coll Cardiol 1994; 23:961–969. 36. Dinh T, Baur LH, Pisters R, et al. Aspirin versus vitamin K antagonist treatment guided by transoesophageal echocardiography in patients with atrial fibrillation: a pilot study. Heart 2014; 100:563–568. 37. Di Biase L, Santangeli P, Anselmino M, et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J Am Coll Cardiol 2012; 60:531–538. 38. Yamamoto M, Seo Y, Kawamatsu N, et al. Complex left atrial appendage morphology and left atrial appendage thrombus formation & in patients with atrial fibrillation. Circ Cardiovasc Imag 2014; 7:337– 343. This interesting study describes the relation between increased number of left atrial appendage lobes and risk of stroke.
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Left atrial volume and function in patients with atrial fibrillation Darryl P. Leong and Hisham Dokainish
Purpose of review This review of emerging approaches to left atrial imaging in atrial fibrillation is relevant because there has been considerable recent development in the noninvasive characterization of left atrial structure and function. Concurrently, the identification and treatment of atrial fibrillation and the prevention of thromboembolism are evolving. Thus, it is timely to summarize how the advances in these two areas might be synergistic in the treatment of atrial fibrillation. Recent findings This article will summarize recent developments in left atrial imaging that play a role in patients with atrial fibrillation, with particular emphasis on echocardiography, and with reference made to important advances in cardiac computed tomography and cardiac magnetic resonance. The evidence that these modalities can predict who will develop atrial fibrillation, who will achieve sustained sinus rhythm after cardioversion or catheter ablation, and who will have thromboembolic risk will be reviewed. Summary Although existing evidence is promising, the clinical role of cardiac imaging to predict atrial fibrillation occurrence, atrial fibrillation recurrence after treatment, and thromboembolism from atrial fibrillation remains to be confirmed in large-scale studies and clinical trials. Keywords atrial fibrillation, echocardiography, imaging, thromboembolism
INTRODUCTION Atrial fibrillation is common and is expected to grow in prevalence due to ageing populations with a greater burden of chronic cardiovascular disease. Advances in cardiac imaging techniques, permitting detailed characterization of atrial morphology and function, can provide insight into the natural history of atrial fibrillation and enhance the prediction of clinical outcomes and response to treatments. The purpose of this review is to summarize recent developments in left atrial imaging that play a role in individualized patient care, with particular emphasis on echocardiography, and with reference made to important advances in cardiac computed tomography (CCT) and cardiac magnetic resonance (CMR).
LEFT ATRIAL REMODELING AND CHANGES IN LEFT ATRIAL FUNCTION IN ATRIAL FIBRILLATION Atrial fibrillation is characterized by a spectrum of pathological changes that may result from ageing and that may be accelerated by disease processes, such as hypertension, ischemic heart disease,
valvular heart disease, and tachycardia. Current understanding of the relationship between the pathophysiologic determinants of atrial fibrillation, ultrastructural and histological changes to the left atrium, and macroscopic left atrial remodeling are largely inferred from animal models. These models suggest that atrial fibrillation may occur on a pathologic continuum beginning with myocytolysis [1] and myocyte dedifferentiation, and culminating with atrial fibrosis [2]. These pathologic processes are associated with both left atrial dilatation and impairment of left atrial mechanical function. Indeed, experimental evidence suggests that left atrial dilatation and mechanical Department of Medicine, Division of Cardiology, McMaster University Hamilton, ON, Canada Correspondence to Hisham Dokainish, MD, FRCPC, FASE, FACC, Associate Professor of Medicine, McMaster University, Director of Echocardiography, Hamilton Health Sciences, 237 Barton St E., CVSRI #C3 111, Hamilton, ON L8L 2X2, Canada. Tel. +1 905 527 4322 ext. 40327; e-mail: [email protected] Curr Opin Cardiol 2014, 29:437–444 DOI:10.1097/HCO.0000000000000088
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KEY POINTS • Left atrial remodeling (dilation) and impaired left atrial function – by 2D and strain echocardiography – is an important predictor of the development of atrial fibrillation in patients at risk. • Left atrial fibrosis – as represented by impaired echocardiographic left atrial strain and delayed enhancement on CMR – is inversely associated with the ability to restore sinus rhythm in patients with atrial fibrillation. • Increasing left atrial volume, decreasing left atrial strain, and different and more complex left atrial appendage morphologies, by echocardiography, have been associated with an increasing risk of stroke.
dysfunction may predispose to atrial fibrillation [3] (as well as resulting from it), thus creating a vicious cycle that acts to perpetuate atrial fibrillation. Moreover, in patients with atrial fibrillation, there is a positive relationship between left atrial size and atrial fibrillation burden, and a negative relationship between left atrial function and atrial fibrillation burden [4]. Accurate evaluation of left atrial volume and function is important in the characterization of individuals with or at risk of atrial fibrillation and in the evaluation of strategies to treat or prevent atrial fibrillation. Recent advances in echocardiographic approaches to assess left atrial size and
function are important in this regard. Three-dimensional (3D) echocardiography has shown close correlation and minimal bias compared with CMR for the measurement of LA volume [5] and is superior to two-dimensional (2D) echocardiography because image foreshortening can be overcome [6] (Fig. 1). Speckle-tracking approaches to assess left atrial myocardial deformation (strain) and rate of deformation (strain rate) reflect the extent of left atrial fibrosis as measured by late-gadolinium enhancement CMR [7]. Three-dimensional echocardiography and speckle-tracking analysis of left atrial function prominently feature in the potential clinical role of assessing left atrial size and function in the recent literature.
LEFT ATRIAL STRUCTURE AND FUNCTION TO PREDICT OCCURRENCE OF ATRIAL FIBRILLATION The prediction of atrial fibrillation in patients with sinus rhythm is desirable because it may provide an opportunity to prevent systemic thromboembolism – a major complication of atrial fibrillation – which is often the first clinical manifestation of atrial fibrillation [8]. Left atrial size has long been recognized as a predictor of incident atrial fibrillation. Among 486 patients with intermittent atrial fibrillation, Flaker et al. [9] showed that left atrial diameter was associated with atrial fibrillation recurrence. In a study of 1655 patients without known atrial fibrillation, a 30% larger left atrial volume was associated with a 43% increased risk of incident
FIGURE 1. Left atrial volume by three-dimensional transthoracic echocardiography. The panel of four images on the left illustrate orthogonal apical views of the left atrium. The three images on the right demonstrate corresponding short-axis views of the left atrium at the levels indicated by the dashed lines. The left atrial volume by three-dimensional echocardiography is calculated at 44.5 ml, which is within normal limits. 438
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atrial fibrillation [10]. These findings have been mirrored by a population-based CCT study of 3905 patients that showed that left atrial area is a strong predictor of incident atrial fibrillation [11]. Although left atrial size can be evaluated echocardiographically by linear dimension, it is recommended that left atrial size be assessed by volume measurement, due to the inaccuracy of linear dimension [12]. Moreover, despite evidence that measurement of left atrial size provides incremental predictive value to clinical factors for the occurrence of atrial fibrillation, it is unclear whether and how this could be translated to clinical practice [13]. Although one can identify individuals who are more likely to have or to develop atrial fibrillation, it is unclear how to monitor for atrial fibrillation. While 3D echocardiography represents a major advance in the echocardiographic measurement of cardiac volumes, it remains to be seen whether this approach to the quantification of left atrial volume will confer an advantage over 2D measurements in risk stratification for the development of atrial fibrillation. Left atrial mechanical dysfunction is an important part of the pathophysiology of atrial fibrillation. However, it can be challenging to noninvasively image the left atrium in the three phases of mechanical function: reservoir, conduit, and contractile (Fig. 2). Consequently, no consensus exists as to the ideal imaging approach to assess left atrial function. Left atrial strain and strain rate, which are measures of left atrial deformation and deformation rate, respectively, hold particular promise. Left atrial strain and strain rate can be measured by either tissue Doppler or speckle-tracking techniques (Figs 3 and 4). Tissue Doppler approaches are more technically demanding and time consuming, whereas speckle-tracking techniques are somewhat easier. In a study of controls and patients with atrial fibrillation using tissue Doppler strain rate, Inaba et al. [14] found significant differences between groups in reservoir and conduit peaks, but could not demonstrate a difference in the atrial contractile peak. In 63 patients with sinus rhythm and 37 patients with atrial fibrillation or atrial flutter, Leong et al. [15] reported that reservoir and atrial contractile strain rate as well as reservoir strain – whether by tissue Doppler or speckle-tracking approaches – differed between the groups, but that speckle-tracking approaches had superior discriminatory ability for the presence of moderate–severe spontaneous echocardiographic contrast on transesophageal echocardiography (TEE). Kojima et al. [16], using velocity vector imaging, found that not only were left atrial volumes larger in patients
with paroxysmal atrial fibrillation compared with those with no history of atrial fibrillation, but also left atrial function in sinus rhythm was worse in the former group even after adjustment for left atrial volume. In a study of individuals more than 50 years of age, left atrial speckle-tracking strain was the best predictor of a composite of incident cardiovascular events, including atrial fibrillation, which developed in 16 (51%) of the cohort after 3.1 1.4 years of follow-up [17]. Among 580 patients without known atrial fibrillation or mitral valve disease, Hirose et al. [18] found that left atrial speckle-tracking strain was the strongest overall predictor of incident atrial fibrillation; left atrial deformation 37% or less exhibited a positive predictive value (95% confidence interval) of 19% (16–22%) and a negative predictive value (95% confidence interval) of 99% (98–100%). In 101 patients with mild mitral stenosis in sinus rhythm and 70 healthy controls, Ancona et al. [19] reported that speckle-tracking reservoir left atrial strain was the best predictor of incident atrial fibrillation, although the optimal discriminatory threshold in this patient population was 17.4%, which differs from the 37% threshold reported by Hirose et al. [18]. In summary, evaluation of left atrial size can help to identify individuals who will develop atrial fibrillation. There is also growing evidence that echocardiographic measurement of left atrial deformation and function may improve risk prediction of incident atrial fibrillation; however, whether left atrial evaluation should be implemented in clinical practice and should prompt strategies to lower thromboembolic risk remain unclear.
LA volume
LAmax
LApreA
LAmin Reservoir function = 100.(LAmax – LAmin)/LAmin Conduit function = 100.(LAmax – LApreA)/LAmax Contractile function = 100.(LApreA – LAmin)/LApreA
FIGURE 2. Phases of left atrial function. LAmax, maximum left atrial volume; LAmin, minimum left atrial volume; LApreA, left atrial volume at the onset of the A wave. Reproduced with permission from [20].
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(a)
(b) RSr
ASr CSr
FIGURE 3. Left atrial strain (a) and strain rate (b) by speckle-tracking echocardiography. The arrow indicates the peak of the white curve that represents averaged segmental strain scores from the left atrium. ASr, atrial contractile strain rate; CSr, conduit strain rate; RSr, reservoir strain rate. Reproduced by permission from Oxford University Press on behalf of the European Society of Cardiology from [15].
LEFT ATRIAL VOLUME AND FUNCTION TO PREDICT SUCCESS OF CARDIOVERSION OF ATRIAL FIBRILLATION Cardioversion of atrial fibrillation may be recommended for selected individuals as part of a longterm strategy of rhythm control [21]. For many, cardioversion of atrial fibrillation is unsuccessful 440
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or atrial fibrillation recurs within a short period of time; thus, a-priori identification of such patients may be useful. In a multicenter European registry, Pisters et al. [22] found that smaller left atrial diameter was independently associated with the long-term maintenance of sinus rhythm after electrical Volume 29 • Number 5 • September 2014
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Left atrial volume and function in patients with atrial fibrillation Leong and Dokainish
(a)
RSr (b)
CSr
ASr
FIGURE 4. Left atrial strain (a) and strain rate (b) by tissue Doppler imaging. The arrow indicates peak left atrial strain. ASr, atrial contractile strain rate; CSr, conduit strain rate; RSr, reservoir strain rate. Reproduced by permission from Oxford University Press on behalf of the European Society of Cardiology from [15].
cardioversion. Di Salvo et al. [23] studied 65 consecutive patients undergoing cardioversion for lone atrial fibrillation, finding that tissue Doppler left atrial strain and strain rate were independent predictors of the maintenance of sinus rhythm over the subsequent 9 months. In a study of patients undergoing pharmacologic cardioversion of atrial fibrillation with intravenous
flecainide, Limantoro et al. [24] found that both the atrial fibrillation cycle length and the atrial fibrillation tissue velocity, by color-coded tissue velocity imaging of the lateral left atrial wall, were reasonable discriminators of the immediate success of pharmacologic cardioversion, with areas under the receiver operating characteristic curve of 0.78 and 0.79, respectively. The clinical
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usefulness of this approach is uncertain, however, because it requires easy access to echocardiography and expertise in performing the required measurements (both of which may be challenging in the emergency department setting) and was only feasible in 55% of patients studied.
LEFT ATRIAL STRUCTURE AND FUNCTION TO PREDICT SUCCESS OF CATHETER ABLATION OF ATRIAL FIBRILLATION Atrial fibrillation ablation may be recommended as a therapeutic approach to symptom control for patients with paroxysmal atrial fibrillation [25]; therefore, imaging predictors of patients who are more likely to derive benefit would be of value. In a study of consecutive patients undergoing atrial fibrillation catheter ablation, Marsan et al. [26] found that preablation left atrial volume index by 3D transthoracic echocardiography was significantly larger in patients who developed atrial fibrillation recurrence (31 8 ml/m2) compared with those who maintained sinus rhythm (26 8 ml/m2; P < 0.05) during 7.9 months’ follow-up. Among 73 patients undergoing atrial fibrillation ablation, Helms et al. [27] found that left atrial volume more than 135 ml, by CCT, had a sensitivity of 36% and specificity of 96% for atrial fibrillation recurrence over 12 months’ follow-up. In a study of patients undergoing a first atrial fibrillation ablation, Marrouche et al. [28 ] demonstrated, using late gadolinium enhancement CMR, that there was a significant relationship between noninvasively quantified left atrial fibrosis and atrial fibrillation recurrence. Schneider et al. [29] measured left atrial dimensions and tissue Doppler strain and strain rate before and 24 h after atrial fibrillation ablation, finding that no preablation clinical or echocardiographic characteristic distinguished patients who would maintain sinus rhythm at 3 months [29]. These findings contrast with those of Hammerstingl et al. [30], who reported that a global left atrial strain threshold of 10.79% in the apical four-chamber view had a positive predictive value of 78.8% and a negative predictive value of 93.9% for the recurrence of atrial fibrillation following catheter ablation. Prior to atrial fibrillation ablation, echocardiography and (for pulmonary vein characterization) either CCT or CMR are often performed. When different estimates of left atrial volume are available, 2D measurements underestimate left atrial volume compared with 3D measurements [31]. Additionally, superior signal-to-noise ratio of CCT or CMR compared with echocardiography may make these more reliable modalities when available. However, further studies of &&
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3D echocardiographic left atrial volume compared with MRI or computed tomography are warranted.
LEFT ATRIAL VOLUME AND FUNCTION TO PREDICT STROKE RISK FROM ATRIAL FIBRILLATION In patients with atrial fibrillation, the benefits of anticoagulation for the prevention of thromboembolism must be weighed against the risk of bleeding. While clinical tools can help predict an individual’s risk of stroke, their discriminatory ability is limited [32]. By detailed left atrial characterization, imaging techniques may further refine stroke risk stratification for patients with atrial fibrillation. In a study of patients with atrial fibrillation, stroke/transient ischemic attack, and CHADS2 scores 1 or lower, and controls with atrial fibrillation but no history of cerebrovascular disease, left atrial speckle-tracking strain was independently associated with stroke [33]. These findings suggest that, in individuals with atrial fibrillation who are thought to have a low stroke risk on clinical grounds, speckletracking strain may help reclassify some individuals into a higher risk group. Indeed, even in a group of patients with permanent atrial fibrillation and higher stroke risk than that seen in the previous study, Shih et al. [34] found that left atrial speckletracking strain and strain rate were independently associated with stroke risk. There is some evidence of an association between left atrial spontaneous echocardiographic contrast/ appendage emptying velocity measured by TEE and left atrial thromboembolism [35]. In a randomized, controlledtrial,randomizing patientswithatrialfibrillation and an indication for anticoagulation to a vitamin K antagonist or aspirin on the basis of TEE findings of left atrial blood stasis or complex aortic plaque [36], aspirin was found to be noninferior to vitamin K antagonist with respect to the primary endpoint of stroke, major bleeding, and peripheral embolism. The left atrial appendage, an important putative source of thromboembolism, has heterogeneous morphology. Di Biase et al. [37] categorized the left atrial appendage into one of four morphologic patterns on the basis of CCT or CMR, performed on 932 patients with atrial fibrillation planned for ablation, finding that stroke risk varied with left atrial appendage type: a ‘Chicken wing’ appendage, typified by a bend in the proximal or middle part of the dominant appendage lobe, was associated with a lower risk of stroke, and a ‘Cauliflower’ appendage, with a more lobulated, complex morphology, was associated with a higher risk of stroke. Using TEE in patients with atrial fibrillation, Yamamoto et al. [38 ] examined the relationship between the number of left atrial appendage &
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lobes and the presence of left atrial appendage thrombus, finding that 94% of patients with left atrial appendage thrombus had at least three left atrial appendage lobes. While the left atrial appendage has been thought to be important in thromboembolism for some time, the technology to move beyond left atrial size to a more refined characterization of chamber morphology, with the goal of thromboembolic risk stratification, has only recently been explored.
CONCLUSION Left atrial volume assessment is important in the prediction of atrial fibrillation occurrence and recurrence after rhythm-control therapies. When available, 3D imaging approaches to left atrial characterization permit more accurate measurement of left atrial volume. Recently, there has been particular growth in research into the role of speckle-tracking strain approaches, in particular, to evaluate left atrial function, and how this evaluation can predict the incidence of atrial fibrillation and potentially guide the treatment of atrial fibrillation; yet, there are significant obstacles to the widespread clinical uptake of left atrial speckle-tracking imaging, such as a paucity of outcomes research, and it remains uncertain whether the use of speckle-tracking should alter clinical practice. Also, multicenter studies, which are important to demonstrate the widespread utility of speckle-tracking outside research institutions, are lacking. Little information is available on intervendor comparability; however, CMR and CCT to assess left atrial structure and function show significant promise in patients with atrial fibrillation and are being increasingly used to understand the optimal risk stratification and management of this important and growing patient population. Acknowledgements None. Conflicts of interest There are no conflicts of interest.
REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the period of review, have been highlighted as: & of special interest && of outstanding interest 1. Ausma J, van der Velden HM, Lenders MH, et al. Reverse structural and gap-junctional remodeling after prolonged atrial fibrillation in the goat. Circulation 2003; 107:2051–2058. 2. Burstein B, Nattel S. Atrial fibrosis: mechanisms and clinical relevance in atrial fibrillation. J Am Coll Cardiol 2008; 51:802–809.
3. Schotten U, de Haan S, Neuberger HR, et al. Loss of atrial contractility is primary cause of atrial dilatation during first days of atrial fibrillation. Am J Physiol Heart Circ Physiol 2004; 287:H2324–H2331. 4. Gupta DK, Shah AM, Giugliano RP, et al. Left atrial structure and function in atrial fibrillation. ENGAGE AF-TIMI 48. Eur Heart J 2013. [Epub ahead of print] 5. Mor-Avi V, Yodwut C, Jenkins C, et al. Real-time 3D echocardiographic quantification of left atrial volume: multicenter study for validation with CMR. JACC Cardiovasc Imag 2012; 5:769–777. 6. Iwataki M, Takeuchi M, Otani K, et al. Measurement of left atrial volume from transthoracic three-dimensional echocardiographic datasets using the biplane Simpson’s technique. J Am Soc Echocardiogr 2012; 25:1319– 1326. 7. Kuppahally SS, Akoum N, Burgon NS, et al. Left atrial strain and strain rate in patients with paroxysmal and persistent atrial fibrillation: relationship to left atrial structural remodeling detected by delayed-enhancement MRI. Circ Cardiovasc Imag 2010; 3:231–239. 8. Lin HJ, Wolf PA, Benjamin EJ, et al. Newly diagnosed atrial fibrillation and acute stroke. The Framingham study. Stroke 1995; 26:1527– 1530. 9. Flaker GC, Fletcher KA, Rothbart RM, et al. Clinical and echocardiographic features of intermittent atrial fibrillation that predict recurrent atrial fibrillation. Stroke Prevention in Atrial Fibrillation (SPAF) investigators. Am J Cardiol 1995; 76:355–358. 10. Tsang TS, Barnes ME, Bailey KR, et al. Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women. Mayo Clin Proc 2001; 76:467–475. 11. Mahabadi AA, Lehmann N, Kalsch H, et al. Association of epicardial adipose tissue and left atrial size on noncontrast CT with atrial fibrillation: the Heinz Nixdorf recall study. Eur Heart J Cardiovasc Imag 2014. [Epub ahead of print] 12. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005; 18:1440–1463. 13. Quinn FR, Gladstone D. Screening for undiagnosed atrial fibrillation in the community. Curr Opin Cardiol 2014; 29:28–35. 14. Inaba Y, Yuda S, Kobayashi N, et al. Strain rate imaging for noninvasive functional quantification of the left atrium: Comparative studies in controls and patients with atrial fibrillation. J Am Soc Echocardiogr 2005; 18:729–736. 15. Leong DP, Penhall A, Perry R, et al. Speckle-tracking strain of the left atrium: a transoesophageal echocardiographic validation study. Eur Heart J Cardiovasc Imag 2013; 14:898–905. 16. Kojima T, Kawasaki M, Tanaka R, et al. Left atrial global and regional function in patients with paroxysmal atrial fibrillation has already been impaired before enlargement of left atrium: velocity vector imaging echocardiography study. Eur Heart J Cardiovasc Imag 2012; 13:227–234. 17. Cameli M, Lisi M, Focardi M, et al. Left atrial deformation analysis by speckle tracking echocardiography for prediction of cardiovascular outcomes. Am J Cardiol 2012; 110:264–269. 18. Hirose T, Kawasaki M, Tanaka R, et al. Left atrial function assessed by speckle tracking echocardiography as a predictor of new-onset nonvalvular atrial fibrillation: results from a prospective study in 580 adults. Eur Heart J Cardiovasc Imag 2012; 13:243–250. 19. Ancona R, Comenale Pinto S. Two-dimensional atrial systolic strain imaging predicts atrial fibrillation at 4-year follow-up in asymptomatic rheumatic mitral stenosis. J Am Soc Echocardiogr 2013; 26:270–277. 20. Leong DP, Delgado V, Bax JJ. Imaging for atrial fibrillation. Curr Probl Cardiol 2012; 37:7–33. 21. Wann LS, Curtis AB, Ellenbogen KA, et al. Management of patients with atrial fibrillation (compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/ AHA/HRS recommendations): a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127:1916–1926. 22. Pisters R, Nieuwlaat R, Prins MH, et al. Clinical correlates of immediate success and outcome at 1-year follow-up of real-world cardioversion of atrial fibrillation: the Euro Heart Survey. Europace 2012; 14:666–674. 23. Di Salvo G, Caso P, Lo Piccolo R, et al. Atrial myocardial deformation properties predict maintenance of sinus rhythm after external cardioversion of recent-onset lone atrial fibrillation: a color Doppler myocardial imaging and transthoracic and transesophageal echocardiographic study. Circulation 2005; 112:387–395. 24. Limantoro I, De Vos CB, Delhaas T, et al. Tissue velocity imaging of the left atrium predicts response to flecainide in patients with acute atrial fibrillation. Heart Rhythm 2014; 11:478–484. 25. Camm AJ, Lip GY, De Caterina R, et al. 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an update of the 2010 ESC guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. Eur Heart J 2012; 33:2719–2747.
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Imaging and echocardiography 26. Marsan NA, Tops LF, Holman ER, et al. Comparison of left atrial volumes and function by real-time three-dimensional echocardiography in patients having catheter ablation for atrial fibrillation with persistence of sinus rhythm versus recurrent atrial fibrillation three months later. Am J Cardiol 2008; 102:847–853. 27. Helms AS, West JJ, Patel A, et al. Relation of left atrial volume from threedimensional computed tomography to atrial fibrillation recurrence following ablation. Am J Cardiol 2009; 103:989–993. 28. Marrouche NF, Wilber D, Hindricks G, et al. Association of atrial tissue && fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: The DECAAF study. JAMA 2014; 311:498–506. This multicenter study demonstrated that left atrial fibrosis as quantified by late gadolinium cardiac magnetic resonance could predict success of catheter ablation for atrial fibrillation, raising the possibility that this technique could be applied in clinical practice in centers without specific expertise in atrial late gadolinium enhancement cardiac magnetic resonance. 29. Schneider C, Malisius R, Krause K, et al. Strain rate imaging for functional quantification of the left atrium: atrial deformation predicts the maintenance of sinus rhythm after catheter ablation of atrial fibrillation. Eur Heart J 2008; 29:1397–1409. 30. Hammerstingl C, Schwekendiek M, Momcilovic D, et al. Left atrial deformation imaging with ultrasound based two-dimensional speckletracking predicts the rate of recurrence of paroxysmal and persistent atrial fibrillation after successful ablation procedures. J Cardiovasc Electrophysiol 2012; 23:247–255. 31. Tops LF, van der Wall EE, Schalij MJ, Bax JJ. Multi-modality imaging to assess left atrial size, anatomy and function. Heart 2007; 93:1461–1470.
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32. Friberg L, Rosenqvist M, Lip GY. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182678 patients with atrial fibrillation: the Swedish atrial fibrillation cohort study. Eur Heart J 2012; 33:1500–1510. 33. Azemi T, Rabdiya VM, Ayirala SR, et al. Left atrial strain is reduced in patients with atrial fibrillation, stroke or TIA, and low risk CHADS(2) scores. J Am Soc Echocardiogr 2012; 25:1327–1332. 34. Shih JY, Tsai WC, Huang YY, et al. Association of decreased left atrial strain and strain rate with stroke in chronic atrial fibrillation. J Am Soc Echocardiogr 2011; 24:513–519. 35. Fatkin D, Kelly RP, Feneley MP. Relations between left atrial appendage blood flow velocity, spontaneous echocardiographic contrast and thromboembolic risk in vivo. J Am Coll Cardiol 1994; 23:961–969. 36. Dinh T, Baur LH, Pisters R, et al. Aspirin versus vitamin K antagonist treatment guided by transoesophageal echocardiography in patients with atrial fibrillation: a pilot study. Heart 2014; 100:563–568. 37. Di Biase L, Santangeli P, Anselmino M, et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J Am Coll Cardiol 2012; 60:531–538. 38. Yamamoto M, Seo Y, Kawamatsu N, et al. Complex left atrial appendage morphology and left atrial appendage thrombus formation & in patients with atrial fibrillation. Circ Cardiovasc Imag 2014; 7:337– 343. This interesting study describes the relation between increased number of left atrial appendage lobes and risk of stroke.
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