|Year : 2014 | Volume
| Issue : 3 | Page : 72-77
Left Atrium: Still a neglected chamber?
Maria Chiara Todaro1, Bijoy K Khandheria2
1 Cardiology Unit, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
2 Aurora Cardiovascular Services, Aurora Sinai/Aurora St. Luke's Medical Centers, University of Wisconsin School of Medicine and Public Health, Wisconsin, USA
|Date of Web Publication||5-Nov-2014|
Bijoy K Khandheria
Aurora Cardiovascular Services 2801W. Kinnickinnic River Parkway, #840
Source of Support: None, Conflict of Interest: None
It is widely recognized that an effective cardiovascular system is based upon both a good ventricular-vascular interplay and a good ventricular-atrial interaction in all the phases of cardiac cycle. Moreover, left atrial dysfunction has been identified to be contributory in several common cardiovascular conditions, such as heart failure, atrial fibrillation and valvular heart disease; for instance, a good anatomical and functional assessment of this cardiac chamber is mandatory. For this purpose a multimodality imaging approach - including two-dimensional and three-dimensional echocardiography, speckle tracking technique, cardiac computed tomography (CT) and cardiac magnetic resonance (CMR) - is the most suitable one to achieve the best functional and anatomical evaluation of this cardiac chamber.
Keywords: Left atrium, multimodality imaging, speckle tracking echocardiography
|How to cite this article:|
Todaro MC, Khandheria BK. Left Atrium: Still a neglected chamber?. J Cardiovasc Echography 2014;24:72-7
| Introduction|| |
The left atrium (LA) plays a pivotal role in the performance of the cardiovascular system; for this reason, a more detailed evaluation of its size and function is gaining importance in the global assessment of patients affected by cardiovascular diseases. 
Left atrial (LA) functional integrity greatly contributes to left ventricular (LV) filling, and thus to the achievement of an effective stroke volume through all the phases of cardiac cycle. For example, the LA acts as a reservoir during LV systole receiving blood from pulmonary veins, as a conduit during early diastole and as a booster pump during late diastole, accounting respectively for 40%, 35% and 25%, of the atrial contribution to stroke volume. 
The role of LA function proved to be contributory in the most common cardiovascular scenarios, from atrial fibrillation recurrence  to heart failure hospitalization rates prediction  and valvular heart diseases prognosis,  prompting cardiologists to be more familiar with noninvasive assessment of LA size and function. Although it may seem obvious, LA evaluation is still a challenge and requires a multimodality approach carried out by experts.
Imaging the left atrium: Why a multimodality approach?
Two-dimensional echocardiography (2DE) and three-dimensional echocardiography (3DE), cardiac computed tomography (CT), and cardiac magnetic resonance (CMR) are the imaging techniques available for the assessment of the LA. 
Since each of them is characterized by different strengths and weaknesses, none can be considered by itself the best imaging modality; conversely, they should be conceived in complementary fashion through a multimodality imaging approach in several clinical settings.
Among the three modalities, echocardiography is most suited to measuring phasic LA volumes because, due to its high temporal resolution, it allows the assessment of LA volumes (active and passive) in all the phases of cardiac cycle and LA ejection fraction [Table 1].
American Society of Echocardiography, in conjunction with the European Association of Echocardiography, recommends the measurement of LA volumes with either an ellipsoid model or the Simpson's method in four- and two-chamber apical views:  Pre-atrial contraction volume (VpreA) is measured at the onset of the P-wave on an electrocardiogram; minimal LA volume (Vmin), measured at the closure of the mitral valve in end-diastole and maximal LA volume (Vmax), measured just before the opening of the mitral valve in end-systole.
However, measurement of LA phasic volumes using 2DE is time consuming; moreover, exact timing of various atrial events can be challenging and geometric assumptions of biplane volume calculations, as well as poor echocardiographic window, may introduce mistakes in LA cavity estimation. 
These limitations can be partially overcome by 3DE that allows acquiring a three-dimensional data set with automated endocardial border tracing. Although temporal resolution of 3DE may be inferior to 2DE, it still remains superior to CT or CMR.  Moreover, although LA volumes derived from 3DE tend to be higher than 2DE LA volumes, they show less intra- and inter-observer variability and good agreement with CMR derived volumes. 
Cardiac CT is characterized by the highest anatomical definition, allowing the acquisition of three-dimensional images that accurately depict LA and pulmonary venous anatomy. For this reason, in some centers it has become the investigation of choice especially for the detection of pulmonary vein anatomical variations before atrial fibrillation ablation.  However, the routine use of cardiac CT solely for the purpose of assessing atrial size and function cannot be recommended, not only because of radiation exposure and the use of iodinated contrast in patients with renal impairment, but also because of technical issues related to CT data acquisition. The low temporal resolution of this technique (75 to 250 ms, 10 times less than echocardiography) represents a major concern, particularly for phasic LA volumes measurement; moreover, image acquisition generally occurs at mid-late ventricular diastole.  As a result, phasic LA volumes cannot be measured, and the measured LA volume is different from the conventional measurement of LAmax at end-ventricular systole. 
Cardiac MR is the criterion-standard technique for LA volumes estimation. It is performed with consecutive multislice breath-hold acquisitions, followed by post-processing with either manual or automated tracing of the atrial wall border.  This technique has been used to establish normal ranges for LA phasic volumes as well as for ejection fractions.  The temporal resolution of CMR (around 25 to 50 ms) is inferior to 2DE, but is sufficient for this purpose. Studies in patients with atrial fibrillation demonstrate that CMR is able to measure LA phasic volumes and LA ejection fraction (LAEF) and to evaluate LA reverse remodeling after pulmonary vein isolation. ,
However, one of the main clinical applications of CMR is the possibility of noninvasive assessment of atrial fibrosis on the basis of delayed contrast enhancement (DCE) distribution, especially for the prediction of atrial fibrillation (AF) recurrence in the post-radiofrequency ablation setting. 
In fact, a larger amount of fibrosis, and so of DCE in the ablation sites, represents a more complete isolation of the AF focus and less chance of recurrence. Moreover, some authors , demonstrated that not only the degree of post-ablation fibrosis within the LA is useful in predicting the outcome of patients, but also that the amount of pre-ablation fibrosis is strongly associated with AF recurrence after pulmonary vein isolation. They observed an AF recurrence rate of 14% in patients with minimal enhancement, 43% in those with moderate enhancement, and 75% in those with extensive enhancement before the procedure.
For this purpose, the Utah classification divides patients into four groups according to degree of fibrosis detected by CMR: Utah I (≤5% LA wall DCE), Utah II (>5 to ≤20% LA wall DCE), Utah III (>20 to ≥35% LA wall DCE), and Utah IV (≥35%).  Catheter ablation proved successful in suppressing AF in all of Utah I, 81.8% of Utah II, in 62.5% of Utah III patients, and none of Utah IV patients; moreover, no recurrence of the arrhythmia occurred in Utah I patients, whereas the rate of recurrence of the arrhythmia was progressively higher according to the increasing amount of fibrosis (28% in Utah II, 35% in Utah III, and 56% in Utah IV). ,
The finding shows how LA tissue characterization, with special regard to LA fibrosis integrated with LA functional evaluation could help in clinical practice to perform a more patient-tailored approach to the arrhythmia.
All imaging modalities offer specific clues to the anatomical assessment, volumes estimation and tissue characterization of LA, and should be used in a complementary fashion in order to obtain the biggest amount of information in several clinical settings.
Left atrial mechanics in "short"
LA function can be non-invasively evaluated through two-dimensional echocardiography, as well as Doppler analysis of the transmitral and pulmonary vein flow and tissue Doppler assessment of LA myocardial velocities. However, quantification of LA function remains a challenge. Tissue Doppler imaging-derived strain is limited by suboptimal reproducibility, angle dependency, and signal artifacts.
Evaluation of LA deformation parameters through speckle tracking echocardiography is a relatively new, promising approach for analyses of phasic LA mechanics. ,
Myocardial strain and strain rate (SR) represent the magnitude and rate, respectively, of myocardial deformation. Strain is a fractional change in the length of a myocardial segment; it is usually expressed as percentage and it can have positive or negative values, which reflect respectively lengthening or shortening of LA walls. SR is the rate of change in strain and corresponds to the speed at which myocardial deformation occurs, expressed per second.
During the cardiac cycle, the LA acts as a reservoir, receiving pulmonary venous return during LV systole; as a conduit, passively transferring blood to the LV during early diastole; and as a pump, actively priming the LV in late diastole.  LV mechanical events occurring during the LA reservoir period, from mitral valve closure to opening, are isovolumic contraction, ejection, and isovolumic relaxation [Figure 1]. The LA reservoir phase is essential for LV filling because the energy stored by the LA during ventricular systole is released after mitral valve opening, greatly contributing to LV stroke volume.  The LA conduit phase includes early LV filling and diastasis. LA contractile phase performance depends on preload, afterload, intrinsic contractility, and electromechanical coupling  [Table 1].
|Figure 1: (Original) Left atrial strain during all the phases of cardiac cycle LAC = Left atrial contraction, IVC = Isovolumic contraction, IVR = Isovolumic relaxation, EF = Early filling|
Click here to view
Due to the complex three-dimensional motion of the heart, two-dimensional speckle tracking is not able to measure all the components of the local displacement, in contrast the recently developed three-dimensional speckle tracking can track the motion of speckles irrespective of their directions combining longitudinal and circumferential strains. ,
What is new on left atrial mechanics?
However, LA mechanics proved to be abnormal in several clinical conditions, even before anatomical changes have occurred. Early detection of LA dysfunction proves to provide new insight into pathophysiology of several conditions such as AF, hypertension, heart failure, and valvular heart disease, in which atrial dysfunction has been identified as an important contributor.
Heart failure with preserved ejection fraction
In heart failure with preserved ejection fraction, LA is chronically exposed to elevated end-diastolic pressure determining both LA enlargement and functional impairment.
In this clinical setting in the absence of other contributing pathology such as mitral valve disease, LA structural and functional remodeling is considered a reliable barometer of diastolic burden and a marker of severity of diastolic dysfunction, and cardiovascular death. 
In this context both reservoir and conduit functions  and recently also 3D LA strain are reduced and show to be accurate for estimation of LV filling pressure. 
Besides these hemodynamic associations, LA strain has been inversely correlated with brain natriuretic peptide level  and worse New York Heart Association functional class. ,
LA pump function presents a biphasic response: In early heart failure it is augmented to compensate for reduced early LV filling, whereas in late stages, as work mismatch progresses, LA contractile properties gradually deteriorate. 
During AF, LA contractile function is lost while both reservoir and conduit functions are reduced, with significant differences between paroxysmal and chronic persistent AF. 
A larger amount of LA fibrosis and as a consequence a higher LA stiffness are both associated with lower values of LA strain, reflecting the inverse relationship existing between LA structural and functional remodeling, especially in patients with chronic AF.
After cardioversion, strain and SR, as well as conventional parameters linked to atrial contractile function, are reduced due to LA stunning;  a gradual recovery of atrial strain generally occurs after cardioversion, with peak improvement within 4 weeks.
Moreover, when it comes to predict the recurrence of the arrhythmia after cardioversion in patients with both paroxysmal and chronic persistent AF, the highest chance of maintaining sinus rhythm during follow-up was detected in patients with better pre-cardioversion values of LA strain and good LA reverse remodeling, if compared with the patients who reverted to AF. 
Moreover, global LA strain has an incremental value when combined with CHADS2 risk score and LA volume index in predicting the hospitalization rate and cardiovascular events. 
Average values of LA systolic strain and SR at baseline are now considered independent predictors of LA reverse remodeling and AF recurrence, with possible future implication in the management of antiarrhythmic drugs and in the selection of candidates for anticoagulant therapy.
Further studies are needed to determine the independent prognostic power of atrial strain as a predictor of future cardiovascular events.
Left atrial mechanics and valvular heart disease
In aortic stenosis, LV diastolic dysfunction associated with LA enlargement adversely affects outcomes. Some investigators , studied the impact of aortic stenosis on LA phasic function and reported that all LA longitudinal strain values are reduced, and that LA booster pump function is particularly affected by the severity of aortic stenosis.
Chronic mitral regurgitation generates LA volume overload and as a result, promotes both anatomical and functional remodeling of this chamber. Higher values of LA strain in all phases of cardiac cycle along with elevated static and dynamic LA volumes have been demonstrated by some authors.  However, others have reported a deterioration of all LA deformation parameters, probably in the latest stages of the disease,  with a further decrease of LA strain in patients with mitral regurgitation and history of recurrent AF. 
The double couple: The atrial-ventricular vascular interplay
An effective and performing cardiovascular system is based upon a good ventricular vascular and atrial-ventricular coupling in all the phases of cardiac cycle.
The interplay between heart and vessels is represented by ventricular-arterial coupling, determined by effective arterial elastance (Ea) and ventricular end-systolic elastance (Ees). The Ea/Ees ratio is known as the ventricular-arterial coupling index and a central determinant of cardiovascular performance. 
Similarly, atrial stiffness can be considered a new marker of atrial-ventricular interplay. It is a dimensionless, strain-derived parameter obtained by the ratio between E/E' and LA strain during reservoir (E/E': LA reservoir). It demonstrated to correlate with invasively measured ventricular end-diastolic pressure and can be considered a new reliable surrogate marker of LV diastolic function.  Atrial stiffness combines LA function evaluated through speckle tracking echocardiography and traditional Doppler estimate of end-diastolic pressure; for this reason it can be considered a new reliable marker of atrial-ventricular interplay. However, further studies are needed to validate the prognostic importance of this parameter in different clinical settings.
| Conclusion|| |
In few years a lot of progress has been done toward a deeper functional and anatomical assessment of the left atrium, whose role in the global cardiovascular system is now widely recognized. New techniques are now available for a comprehensive evaluation of this chamber and a multimodality imaging approach is considered the best one for this purpose.
For instance, we can now affirm that the left atrium is no longer a "neglected" chamber.
| Acknowledgements|| |
The authors gratefully acknowledge Susan Nord and Jennifer Pfaff of Aurora Cardiovascular Services for the editorial preparation of the manuscript and Brian J. Miller and Brian Schurrer of Aurora Sinai Medical Center for help with the figures.
| References|| |
|1.||Cianciulli TF, Saccheri MC, Lax JA, Bermann AM, Ferreiro DE. Two-dimensional speckle tracking echocardiography for the assessment of atrial function. World J Cardiol 2010;2:163-70. |
|2.||Todaro MC, Choudhuri I, Belohlavek M, Jahangir A, Carerj S, Oreto L, et al. New echocardiographic techniques for evaluation of left atrial mechanics. Eur Heart J Cardiovasc Imaging 2012;13:973-84. |
|3.||Schneider C, Malisius R, Krause K, Lampe F, Bahlmann E, Boczor S, 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;29:1397-409. |
|4.||Eicher JC, Laurent G, Mathé A, Barthez O, Bertaux G, Philip JL, et al. Atrial dyssynchrony syndrome: An overlooked phenomenon and a potential cause of 'diastolic' heart failure. Eur J Heart Fail 2012;14:248-58. |
|5.||O'Connor K, Magne J, Rosca M, Piérard LA, Lancellotti P. Impact of aortic valve stenosis on left atrial phasic function. Am J Cardiol 2010;106:1157-62. |
|6.||To AC, Flamm SD, Marwick TH, Klein AL. Clinical utility of multimodality LA imaging: Assessment of size, function, and structure. JACC Cardiovasc Imaging 2011;4:788-98. |
|7.||Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al.; Chamber Quantification Writing Group; American Society of Echocardiography's Guidelines and Standards Committee; European Association of Echocardiography. 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;18:1440-63. |
|8.||Jenkins C, Bricknell K, Marwick TH. Use of real-time three-dimensional echocardiography to measure left atrial volume: Comparison with other echocardiographic techniques. J Am Soc Echocardiogr 2005;18:991-7. |
|9.||Poutanen T, Ikonen A, Vainio P, Jokinen E, Tikanoja T. Left atrial volume assessed by transthoracic three dimensional echocardiography and magnetic resonance imaging: Dynamic changes during the heart cycle in children. Heart 2000;83:537-42. |
|10.||Lin FY, Devereux RB, Roman MJ, Meng J, Jow VM, Jacobs A, et al. Cardiac chamber volumes, function, and mass as determined by 64-multidetector row computed tomography: Mean values among healthy adults free of hypertension and obesity. JACC Cardiovasc Imaging 2008;1:782-6. |
|11.||Wolf F, Ourednicek P, Loewe C, Richter B, Gössinger HD, Gwechenberger M, et al. Evaluation of left atrial function by multidetector computed tomography before left atrial radiofrequency-catheter ablation: Comparison of a manual and automated 3D volume segmentation method. Eur J Radiol 2010;75:e141-6. |
|12.||Mahabadi AA, Truong QA, Schlett CL, Samy B, O'Donnell CJ, Fox CS, et al. Axial area and anteroposterior diameter as estimates of left atrial size using computed tomography of the chest: Comparison with 3-dimensional volume. J Cardiovasc Comput Tomogr 2010;4:49-54. |
|13.||Hundley WG, Bluemke DA, Finn JP, Flamm SD, Fogel MA, Friedrich MG, et al.; American College of Cardiology Foundation Task Force on Expert Consensus Documents. ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: A report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents. J Am Coll Cardiol 2010;55:2614-62. |
|14.||Hudsmith LE, Cheng AS, Tyler DJ, Shirodaria C, Lee J, Petersen SE, et al. Assessment of left atrial volumes at 1.5 Tesla and 3 Tesla using FLASH and SSFP cine imaging. J Cardiovasc Magn Reson 2007;9:673-9. |
|15.||Therkelsen SK, Groenning BA, Svendsen JH, Jensen GB. Atrial and ventricular volume and function evaluated by magnetic resonance imaging in patients with persistent atrial fibrillation before and after cardioversion. Am J Cardiol 2006;97:1213-9. |
|16.||Wylie JV Jr, Peters DC, Essebag V, Manning WJ, Josephson ME, Hauser TH. Left atrial function and scar after catheter ablation of atrial fibrillation. Heart Rhythm 2008;5:656-62. |
|17.||Longobardo L, Todaro MC, Zito C, Piccione MC, Di Bella G, Oreto L, et al. Role of imaging in assessment of atrial fibrosis in patients with atrial fibrillation: State-of-the-art review. Eur Heart J Cardiovasc Imaging 2014;15:1-5. |
|18.||Oakes RS, Badger TJ, Kholmovski EG, Akoum N, Burgon NS, Fish EN, et al. Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation. Circulation 2009;119:1758-67. |
|19.||Seitz J, Horvilleur J, Lacotte J, O H-Ici D, Mouhoub Y, Maltret A, et al. Correlation between AF substrate ablation difficulty and left atrial fibrosis quantified by delayed-enhancement cardiac magnetic resonance. Pacing Clin Electrophysiol 2011;34:1267-77. |
|20.||Mahnkopf C, Badger TJ, Burgon NS, Daccarett M, Haslam TS, Badger CT, et al. Evaluation of the left atrial substrate in patients with lone atrial fibrillation using delayed-enhanced MRI: Implications for disease progression and response to catheter ablation. Heart Rhythm 2010;7:1475-81. |
|21.||Akoum N, Daccarett M, McGann C, Segerson N, Vergara G, Kuppahally S, et al. Atrial fibrosis helps select the appropriate patient and strategy in catheter ablation of atrial fibrillation: A DE-MRI guided approach. J Cardiovasc Electrophysiol 2011;22:16-22. |
|22.||Daccarett M, McGann CJ, Akoum NW, MacLeod RS, Marrouche NF. MRI of the left atrium: Predicting clinical outcomes in patients with atrial fibrillation. Expert Rev Cardiovasc Ther 2011;9:105-11. |
|23.||Sirbu C, Herbots L, D'hooge J, Claus P, Marciniak A, Langeland T, et al. Feasibility of strain and strain rate imaging for the assessment of regional left atrial deformation: A study in normal subjects. Eur J Echocardiogr 2006;7:199-208. |
|24.||Cameli M, Caputo M, Mondillo S, Ballo P, Palmerini E, Lisi M, et al. Feasibility and reference values of left atrial longitudinal strain imaging by two-dimensional speckle tracking. Cardiovasc Ultrasound 2009;7:6. |
|25.||Mochizuki A, Yuda S, Oi Y, Kawamukai M, Nishida J, Kouzu H, et al. Assessment of left atrial deformation and synchrony by three-dimensional speckle-tracking echocardiography: Comparative studies in healthy subjects and patients with atrial fibrillation. J Am Soc Echocardiogr 2013;26:165-74. |
|26.||Douglas PS. The left atrium: A biomarker of chronic diastolic dysfunction and cardiovascular disease risk. J Am Coll Cardiol 2003;42:1206-7. |
|27.||Wakami K, Ohte N, Asada K, Fukuta H, Goto T, Mukai S, et al. Correlation between left ventricular end-diastolic pressure and peak left atrial wall strain during left ventricular systole. J Am Soc Echocardiogr 2009;22:847-51. |
|28.||Akita N, Ohte N, Wakami K, Kikuchi S, Ikehara N, Fujita H, et al. Left atrial endocardial surface area strain assessed by 3-dimensional speckle tracking imaging is a useful method in assessing left ventricular end-diastolic pressure. Circulation 2011;124:A15077. |
|29.||Kurt M, Tanboga IH, Aksakal E, Kaya A, Isik T, Ekinci M, et al. Relation of left ventricular end-diastolic pressure and N-terminal pro-brain natriuretic peptide level with left atrial deformation parameters. Eur Heart J Cardiovasc Imaging 2012;13:524-30. |
|30.||Morris DA, Gailani M, Vaz Pérez A, Blaschke F, Dietz R, Haverkamp W, et al. Left atrial systolic and diastolic dysfunction in heart failure with normal left ventricular ejection fraction. J Am Soc Echocardiogr 2011;24:651-62. |
|31.||Crea P, Zito C, Cusmà Piccione M, Arcidiaco S, Todaro MC, Oreto L, et al. The role of echocardiography in the evaluation of cardiac damage in hypertensive obese patient. High Blood Press Cardiovasc Prev 2014. [Epub ahead of print]. |
|32.||Kuppahally SS, Akoum N, Burgon NS, Badger TJ, Kholmovski EG, Vijayakumar S, 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 Imaging 2010;3:231-9. |
|33.||Kaya EB, Tokgözoglu L, Aytemir K, Kocabas U, Tülümen E, Deveci OS, et al. Atrial myocardial deformation properties are temporarily reduced after cardioversion for atrial fibrillation and correlate well with left atrial appendage function. Eur J Echocardiogr 2008;9:472-7. |
|34.||Saha SK, Anderson PL, Caracciolo G, Kiotsekoglou A, Wilansky S, Govind S, et al. Global left atrial strain correlates with CHADS2 risk score in patients with atrial fibrillation. J Am Soc Echocardiogr 2011;24:506-12. |
|35.||O'Connor K, Magne J, Rosca M, Piérard LA, Lancellotti P. Left atrial function and remodelling in aortic stenosis. Eur J Echocardiogr 2011;12:299-305. |
|36.||Borg AN, Pearce KA, Williams SG, Ray SG. Left atrial function and deformation in chronic primary mitral regurgitation. Eur J Echocardiogr 2009;10:833-40. |
|37.||Cameli M, Lisi M, Giacomin E, Caputo M, Navarri R, Malandrino A, et al. Chronic mitral regurgitation: Left atrial deformation analysis by two-dimensional speckle tracking echocardiography. Echocardiography 2011;28:327-34. |
|38.||Cameli M, Lisi M, Righini FM, Focardi M, Alfieri O, Mondillo S. Left atrial speckle tracking analysis in patients with mitral insufficiency and history of paroxysmal atrial fibrillation. Int J Cardiovasc Imaging 2012;28:1663-70. |
|39.||Little WC, Pu M. Left ventricular-arterial coupling. J Am Soc Echocardiogr 2009;22:1246-8. |
|40.||Machino-Ohtsuka T, Seo Y, Tada H, Ishizu T, Machino T, Yamasaki H, et al. Left atrial stiffness relates to left ventricular diastolic dysfunction and recurrence after pulmonary vein isolation for atrial fibrillation. J Cardiovasc Electrophysiol 2011;22:999-1006. |