Left Atrial Phasic Function Remodeling During Its Enlargement: a Two-dimensional Speckle-tracking Echocardiography Study

Abstract

Background: Left atrial (LA) size is often used as a surrogate marker of LA function in clinical practice, with larger atria thought to represent a “dysfunctioning” atrium, since there is no accepted ‘gold’ standard to evaluate LA function. The exact relationship between LA size and phasic function, and whether LA dysfunction occur before LA enlargement (LAE) may be of clinical interest while have not been fully studied. Two-dimensional speckle-tracking echocardiography (2D STE) was showed a promising method in measuring LA physic deformation.

Materials and methods: A community cohort of 715 subjects at cardiovascular disease high risk accepted comprehensive echocardiography. LA longitudinal phasic strain Sa (absolute peak strain during atrial contraction), Se (peak strain at early diastole) and Stot (total atrial strain =Sa+Se), representing contractile, conduit, and reservoir function respectively, were measured using off-line 2D STE software in apical 4 chamber view, and data were compared among groups at different LA size and between sub-groups in normal LA size with and without hypertension (HT). 

Results: With LAE (from normal size, mild, moderate to severe LAE), the Stot(21.74±5.97,20.75±4.99,20.49±5.27,17.75±4.71, respectively, ANOVA p=0.003) and Sa (11.84±3.92,11.00±3.29,10.11±2.57,8.55±2.88, respectively, ANOVA p<0.001) reduced while Se had no change. In normal sized LA subgroups, Stot (21.35±5.91 vs 23.01±6.02, p=0.008) and Se (9.51±4.41 vs 11.17±4.89, p<0.001) reduced in subjects with HT comparing with those without.

Conclusion: LA phasic function remodeling occurs before LAE and continues with LAE, with reservoir, conduit and contractile function being affected unparalleled. 

Introduction

The left atrium (LA) plays an integral role in cardiac performance by modulating left ventricular (LV) filling with its reservoir, conduit, and contractile functions^[1]. In clinical practice, LA size, an essential component of echocardiographic parameters, is easily available and widely used as a surrogate marker of its function and regarded as a powerful predictor for adverse clinical outcomes of cardiovascular diseases (CVD)^[2–8]. However, the application of a simple geometric model to a nonsymmetrical chamber in echocardiography to assess LA enlargement (LAE) is actually indirect and limited.

Recently, more and more attention are paid to LA function. Abundant evidences seemed to indicate that LA functional parameters might be surrogate markers of unfavourable cardiovascular outcomes as well^[9–13]. Atrial strain, as an adjunctive measurement of LA function, is an emerging parameter of interest and has been shown to be less load dependent than traditional parameters^[14–16]. However, much less data are available regarding direct relationship between LA size and its phasic function for there is currently no recognized ‘gold’ standard method in LA function assessment^[15].

Therefore, we assessed LA phasic strain with two-dimensional speckle-tracking echocardiography (2D STE) in a high CVD risk community population to explore the relationship between LA phasic function and LA size to answer two questions: (1) Does the larger LA size means worse function? And how do the phasic components change during the period of LAE? (2) Is normal LA size equal to normal function?

Materials And Methods

Study population

A community cohort^[17] screened for CVD and risk factors in urban Beijing was set up in 2005 and 1058 subjects were included. In 2009, subjects were followed up by screening detailed medical history of known CVD, cardiovascular risk factors, and medication history. Height, weight, heart rate and blood pressure were recorded, and routine blood tests were performed.

770 subjects with high risk of CVD accepted comprehensive echocardiography examination. Subjects were defined as high risk of CVD if they had cardiovascular events including myocardial infarction, stroke and peripheral arterial disease, or had at least 2 risk factors including age ≥ 50 years, smoking (current smoker), obesity (BMI≥28), HT, diabetes mellitus (DM) and hyperlipoidemia (total cholesterol > 5.20mmol/L). The 2009 cross-sectional data of 770 subjects were used in this study. All participants provided written informed consent, and the study protocol was approved by the ethics committee of both Peking University and Peking University First Hospital. The study was conducted in accordance with the Declaration of Helsinki.

Echocardiography exam

Comprehensive transthoracic echocardiography was performed on a Vivid 7 ultrasound machine (Vingmed-General Electric, Horten, Norway), using a 1.5–4 MHz phased array transducer. Echocardiographs (with 2D image frame rate over 50 frames/second) with 3 consecutive beats were digitally recorded and analyzed using a customized off-line analyzing software package (Echo PAC, version 110, Vingmed-General Electric). All images and measurements were acquired from the standard views according to the guidelines of the American Society of Echocardiography^[18-20].

LA volume was measured using the biplane method of discs at end systole (just before mitral valve opening). The maximum LA volume was indexed by dividing the body surface area(BSA) to acquire the LA volume index (LAVI)^[21]. Pulmonary artery systolic pressure (PASP) was determined through the tricuspid regurgitation velocity gradient and inferior vena cava size and reactivity. LV ejection fraction (LVEF) (determined by linear Teichholz method) and global longitudinal strain (LV_Slong, averaged strain measured in apical longitudinal, 4-chamber and 2-chamber view by 2D STE) were used as LV systolic parameters. LV diastolic parameter measurements included the ratio of mitral inflow early (E) and late (A) diastolic velocity (E/A), septal mitral annular early (E’) and late (A’) diastolic velocity, and E/E’.

LA phasic strain by 2D STE

Global LA strain were analyzed in apical 4-chamber view 2D image using commercialized software. 2D image of a representative cardiac cycle was selected, and the LA endocardial surface was manually traced by a point-and-click approach. An epicardial surface tracing was automatically generated by the system, creating a region of interest (ROI), which was manually adjusted to cover the full thickness of the LA wall. The software divided the ROI into 6 segments and generated segmental as well as global longitudinal LA strain curves. The onset of the P wave of the superimposed ECG was used as the reference point, which enabled the recognition of absolute peak strain during atrial contraction (Sa), peak strain at early diastole (Se) and total atrial strain (Stot=Sa+Se) in strain curve (Fig. 1). Sa was corresponding to LA contractile, Stot to reservoir and Se to conduit function, respectively^[22-24].

Repeatability and reproducibility

15 randomly selected cases were re-measured by the same observer blinded to previous measurements with 1 week interval, and by a second observer blinded to the first one’s results to assess intra- and inter- observer variability.

Statistical analysis

Data were analyzed with the use of the statistical packages R (The R foundation; http://www.r-project.org; version 3.4.3) and Empower (R) (www.empowerstates.com, X&Y solutions, inc. Boston, Massachusetts). Continuous variables were presented as mean±standard deviation (SD) and categorical variables as percentage rate (%). One-way ANOVA was used to compare continuous variables among groups. Student t test was used in comparison between 2 groups. A Chi-square test was used to compare categorical values between groups. Univariate correlation followed multiple linear regression analyses were performed to examine the association of select clinical variables and echocardiographic findings with LA phasic strain indexes. P-value less than 0.05 were considered statistically significant.

Results

LA phasic strain in different LA size group

The comparison of LA strain among the study groups is shown in Table 3. Reservoir (Stot) indexes are different among groups (P =0.003) with the trend of the larger LA size the lower strain values. While contractile (Sa) indexes are maintained in mild and moderate LAE comparing with normal LA size group, but decreased in severe LAE group (P<0.001). The conduit (Se) indexes are similar among different LA size groups.

LA phasic strain between HT and non-HT groups with normal LA size

Within normal LA size group, subjects were further divided into HT and non-HT subgroups. The HT group had higher prevalence of stroke (23.91% vs. 10.17%, p<0.001) and obesity (23.65% vs. 9.32%, p<0.001) comparing with non-HT group. Differences between HT and non-HT group were also found in age (66.56±8.82 vs. 64.00±9.78years, p=0.007), body mass index (25.91±3.30 vs. 24.44±3.00 kg/ m2, p<0.001), LVMI (84.94±20.10 vs. 78.11±19.10 g/m2, p=0.001), A velocity(96.85±18.35 vs. 85.81±19.65 cm/s, p<0.001), E’ (5.76±1.63 vs. 7.12±2.29 cm/s, p<0.001), E/A (0.80±0.21 vs. 0.94±0.31, p<0.001) and E/e’ (13.80±4.10 vs. 11.67±3.67, p<0.001). There were no differences in other clinical and echocardiographic parameters. The comparison of clinical data and LA strain is shown in Table 4. Reservior (Stot) and conduit (Se) indexes are worse in HT than non-HT subgroup, while contractile (Sa) index has no difference.

Clinical and echocardiographic correlates of LA phasic strain and LAVI: regression analysis

Univariate correlations of LA strain includes demographic parameters (age, gender, body mass index, body surface area, heart rate, SBP and DBP), CVD (myocardial infarction, stroke, peripheral arterial disease), risk factors (HT, HT duration, grade of HT DM, smoke, obesity and hyperlipidemia) and echocardiographic variables (LAVI, LVEDD, LVMI, LVEF and LVSlong, E/A, E/e’, E’, A’ and PASP). Stepwise multiple regression analysis showed that the independent determinants were: for Stot — age, DM, smoking, dyslipidemia, LVSlong and A’ ; for Se — HR, dyslipidemia, LVSlong and E’ ; and for Sa — age, gender, smoking,LAVI༌LVSlong༌E/A༌E’ and A’. (Table 5).

Repeatability and reproducibility

The intra-observer intraclass correlation coefficient (ICC) and absolute difference for 2D STE measurements were Stot 0.97(1.62±1.45%), Se 0.98(1.43±0.76%) and Sa 0.92(1.17±0.99 %). And inter observer ICC and absolute difference were Stot 0.93 (2.07±1.73%), Se 0.89 (2.50±2.35%) and Sa 0.88 (1.76±1.23%), respectively.

Discussion

This cross-sectional study is aimed at exploring the relationship between LA phasic function (phasic strain measured by 2D STE) and LA size in a high cardiovascular risk community population, which is of clinical value for understanding LA performance and pathophysiology. In sum, evidences showed that LA reservoir index (Stot) deteriorates with LA enlargement, contractile index (Sa) maintains in mild/moderate LAE and damaged in sever LAE, conduit index (Se) roughly unchanged during LAE, suggesting that LAE is accompanied with redistributed phasic function. Moreover, compared with non-HT subjects, LA conduit (Se) and reservoir (Stot) indexes are damaged in HT participants with normal LA size, which supports that normal LA size may not be equal to normal function.

LA is far from being a simple passive transport chamber. LA functions as a reservoir during LV systole and isovolumic relaxation, receiving blood from the pulmonary veins and storing energy in the form of pressure. This atrial function is modulated by LV contraction, through the descent of the LV base during systole, by right ventricular systolic pressure transmitted through the pulmonary circulation, and by LA properties (ie, relaxation and chamber stiffness)^[25]. LAVI is the only LA parameter evaluated in general clinical practice to reflect LA function. However, LA strain can also be used as a surrogate measurement of LA function^[26] and prior studies showed that it might be a predictor of adverse outcomes among HT patients^{[3, 27]} or other CVD high risk patients^{[11, 13, 28, 29]}. A 7.9 year follow-up study^[30] showed that LA reservoir and conduit strains were impaired in the stroke compared with non-stroke group with similar LAV. Another longitudinal study^[31] also provided support for LA strain’s prediction value to new-onset AF in heart failure patients. In a community-based general population study, LA reservoir strain below 23% was proved to be an independent predictor of cardiac events including AF, acute coronary syndrome, heart failure^[9]. Daniel et al. reported that abnormal LA strain was observed in patients of left ventricular diastolic dysfunction with normal LAVI^[10]. Moreover, worse LA strain was significantly related to worse New York Heart Association functional class, even in the participants with normal LAVI^[10]. These recent studies demonstrate that LA strain (LA phasic function) might be of high clinical significance, relatively sensitive and superior to LAVI in measuring and detecting unfavorable outcomes.

Figure 2 draws the spectrum of the LA structural and functional remodeling from normal size to sever LAE by phasic strain. The reservoir function (Stot) was impaired under stressors (i.e. HT in this population) even before LAE, and continues to deteriorate with advanced (moderate to severe) LAE, which may indicate that not only wall stretching (which meet the Frank-Starling law, e.g., LA Strain impaired in advanced stretching) but also potential histological change (e. g., fibrosis in HT) can be reflected by LA strain. The conduit function (Se) is damaged in HT subjects before LAE, and remain unchanged during gradually LA enlargement, which suggests Se correlates more with pathophysiological condition rather than LA size. The possible reason is that the conduit is a passive presses relying on LV relaxation and relatively not affected by LA structural remodeling, so in this population we observed no difference of Se among normal size and LAE groups, while in subgroup analysis it reduced in HT subjects, which commonly impair LV relaxation. For contractile function (Sa), it maintained (if not enhanced) until moderate to severe LA dilatation. Many previous researches focused on LA function in HT patients. Miyoshi et al. found LA reservoir and conduit function reduced in HT patients than in controls, but LA contractile function was similar in the two groups^[32]. However, another Chinese cross-sectional study reported that these three function of LA all impaired in HT group^[33]. Disparities among these reports may be result from different grade of HT, age, duration of HT, grade of HT, medication and the control of blood pressure^[34–35].

In short, LA strain (Stot, Se, Sa) are relatively well-characterized surrogate marker of atrial function which plays an essential role in early detection of subclinical LA dysfunction^[13,36−39]. This cross-sectional study provides incremental evidence over prior papers by the direct analysis of the association between LA size and function, as well as by the evaluation of the order of presence of LA dysfunction and LAE in HT patients. At present, despite more and more studies focus on these echo parameters, risk stratification and clinical strategies do not exploited them into clinical practice at present. Evidences concerning the spectrum of LA phasic function provide new insights and useful adjunctive information into the recognition of LA function and structure, especially in HT patients. LA strain (LA phasic function) might be promising predictors in the future.

Limitation

The off line 2D STE software used in this study was not verified by other standard method in LA phasic function evaluation. We used only apical 4 chamber view in LA function evaluation instead averaging 2 or 3 apical views data as other authors did, while the data should be comparable among groups in deducing our results. And we used the image database stored in standard views, while the LA and LV may not coaxial in the long axis, so the precise designed study in LA analysis should collect images focusing on LA. The clinical and prospective significance of LA phasic function remodeling needs to be confirmed in future studies.

Conclusions

In this high cardiovascular risk community population study, we find that LA phasic function remodeling occurs before LA enlargement and continues with LAE. LA reservoir function is impaired under stressors (i.e. HT in this population) before LAE, and continues to deteriorate with advanced (moderate to severe) LAE. The conduit function is damaged (in HT subjects) before LAE, while remain unchanged during gradually LA enlargement. The LA contractile function maintains in mild and moderate LAE while decreases in severe LAE.

Abbreviations

LA: Left atrial; LAE: LA enlargement; 2D STE: Two-dimensional speckle-tracking echocardiography; HT: hypertension; LV: left ventricular; CVD: cardiovascular diseases; BMI: Body mass index; DM: diabetes mellitus; BSA: body surface area; LAVI: LA volume index; PASP: Pulmonary artery systolic pressure; LVEF: LV ejection fraction; ROI: region of interest; SD: standard deviation; ICC: intraclass correlation coefficient.

Declarations

Acknowledgements

None.

Authors’ contributions

Chen CY: data analysis/interpretation, statistics, drafting article; Yang Y: concept/design, data collection, critical revision and approval of article; Zhang Y: concept/design, critical revision and approval of article.

Funding

None.

Availability of data and materials

The data and materials used in this study are available from the corresponding author on reasonable request.

Ethics approval and consent to participate

The study was approved by the ethics committee of both Peking University and Peking University First Hospital. and all subjects gave informed consent.

Consent for publication

All authors and participants consented in writing to publication of this study.

Competing interests

The authors declare that they have no competing interests.

References

1. 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(7):788-798.
2. Peterson TJ, Khawaja FJ, Kane GC, Pellikka PA, McCully RB: Does normal left atrial size really predict normal stress echocardiographic results? J AM COLL CARDIOL 2013, 61(23):2391-2392.
3. Sun T, Xie T, Zhang A, Fan L, Xu Z, Chen X, Fan Z, Wang C: Relation between left atrial structure and lacunar infarction in patients with hypertension. Aging (Albany NY) 2020, 12(17):17295-17304.
4. Milan A, Puglisi E, Magnino C, Naso D, Abram S, Avenatti E, Rabbia F, Mulatero P, Veglio F: Left atrial enlargement in essential hypertension: role in the assessment of subclinical hypertensive heart disease. Blood Press 2012, 21(2):88-96.
5. Hoit BD: Left atrial size and function: role in prognosis. J AM COLL CARDIOL 2014, 63(6):493-505.
6. Gupta DK, Shah AM, Giugliano RP, Ruff CT, Antman EM, Grip LT, Deenadayalu N, Hoffman E, Patel I, Shi M et al: Left atrial structure and function in atrial fibrillation: ENGAGE AF-TIMI 48. EUR HEART J 2014, 35(22):1457-1465.
7. Carluccio E, Dini FL, Biagioli P, Lauciello R, Simioniuc A, Zuchi C, Alunni G, Reboldi G, Marzilli M, Ambrosio G: The 'Echo Heart Failure Score': an echocardiographic risk prediction score of mortality in systolic heart failure. EUR J HEART FAIL 2013, 15(8):868-876.
8. Xue J, Xu XS, Zhu XQ, Li ZZ, Zhang XG, Ma YT, Yang WH, Liu LY, Yue YH: Left Atrial Enlargement is Associated with Stroke Severity with Cardioembolic and Cryptogenic Subtypes in a Chinese Population. J Stroke Cerebrovasc Dis 2020, 29(5):104767.
9. Cauwenberghs N, Haddad F, Sabovčik F, Kobayashi Y, Amsallem M, Morris DA, Voigt JU, Kuznetsova T: Subclinical left atrial dysfunction profiles for prediction of cardiac outcome in the general population. J HYPERTENS 2020, 38(12):2465-2474.
10. Morris DA, Belyavskiy E, Aravind-Kumar R, Kropf M, Frydas A, Braunauer K, Marquez E, Krisper M, Lindhorst R, Osmanoglou E et al: Potential Usefulness and Clinical Relevance of Adding Left Atrial Strain to Left Atrial Volume Index in the Detection of Left Ventricular Diastolic Dysfunction. JACC Cardiovasc Imaging 2018, 11(10):1405-1415.
11. Sargento L, Vicente SA, Longo S, Lousada N, Palma DRR: Left atrial function index predicts long-term survival in stable outpatients with systolic heart failure. Eur Heart J Cardiovasc Imaging 2017, 18(2):119-127.
12. Carluccio E, Biagioli P, Mengoni A, Francesca CM, Lauciello R, Zuchi C, Bardelli G, Alunni G, Coiro S, Gronda EG et al: Left Atrial Reservoir Function and Outcome in Heart Failure With Reduced Ejection Fraction. Circ Cardiovasc Imaging 2018, 11(11): e7696.
13. Russo C, Jin Z, Homma S, Rundek T, Elkind M, Sacco RL, Di Tullio MR: LA Phasic Volumes and Reservoir Function in the Elderly by Real-Time 3D Echocardiography: Normal Values, Prognostic Significance, and Clinical Correlates. JACC Cardiovasc Imaging 2017, 10(9):976-985.
14. Cameli M, Mandoli GE, Loiacono F, Sparla S, Iardino E, Mondillo S: Left atrial strain: A useful index in atrial fibrillation. INT J CARDIOL 2016, 220:208-213.
15. Hoit BD: Assessment of Left Atrial Function by Echocardiography: Novel Insights. CURR CARDIOL REP 2018, 20(10):96.
16. Cameli M, Mandoli GE, Loiacono F, Dini FL, Henein M, Mondillo S: Left atrial strain: a new parameter for assessment of left ventricular filling pressure. HEART FAIL REV 2016, 21(1):65-76.
17. Liu L, Zhao F, Yang Y, Qi LT, Zhang BW, Chen F, Ciren D, Zheng B, Wang SY, Huo Y et al: The clinical significance of carotid intima-media thickness in cardiovascular diseases: a survey in Beijing. J HUM HYPERTENS 2008, 22(4):259-265.
18. Cheitlin MD, Alpert JS, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, Davidson TW, Davis JL, Douglas PS, Gillam LD: ACC/AHA Guidelines for the Clinical Application of Echocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of Echocardiography). Developed in collaboration with the American Society of Echocardiography. CIRCULATION 1997, 95(6):1686-1744.
19. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T et al: Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015, 28(1):1-39.
20. Quiñones MA, Otto CM, Stoddard M, Waggoner A, Zoghbi WA: Recommendations for quantification of Doppler echocardiography: a report from the Doppler Quantification Task Force of the Nomenclature and Standards Committee of the American Society of Echocardiography. J Am Soc Echocardiogr 2002, 15(2):167-184.
21. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T et al: Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 2015, 16(3):233-270.
22. Boyd AC, Richards DA, Marwick T, Thomas L: Atrial strain rate is a sensitive measure of alterations in atrial phasic function in healthy ageing. HEART 2011, 97(18):1513-1519.
23. Saraiva RM, Demirkol S, Buakhamsri A, Greenberg N, Popović ZB, Thomas JD, Klein AL: Left atrial strain measured by two-dimensional speckle tracking represents a new tool to evaluate left atrial function. J Am Soc Echocardiogr 2010, 23(2):172-180.
24. Sun JP, Yang Y, Guo R, Wang D, Lee AP, Wang XY, Lam YY, Fang F, Yang XS, Yu CM: Left atrial regional phasic strain, strain rate and velocity by speckle-tracking echocardiography: normal values and effects of aging in a large group of normal subjects. INT J CARDIOL 2013, 168(4):3473-3479.
25. Rosca M, Lancellotti P, Popescu BA, Piérard LA: Left atrial function: pathophysiology, echocardiographic assessment, and clinical applications. HEART 2011, 97(23):1982-1989.
26. Cameli M, Lisi M, Focardi M, Reccia R, Natali BM, Sparla S, Mondillo S: Left atrial deformation analysis by speckle tracking echocardiography for prediction of cardiovascular outcomes. AM J CARDIOL 2012, 110(2):264-269.
27. Zhao Y, Sun Q, Han J, Lu Y, Zhang Y, Song W, Cheng Y, Cong T, Liu Y, Jiang Y: Left atrial stiffness index as a marker of early target organ damage in hypertension. HYPERTENS RES 2021, 44(3):299-309.
28. Gupta S, Matulevicius SA, Ayers CR, Berry JD, Patel PC, Markham DW, Levine BD, Chin KM, de Lemos JA, Peshock RM et al: Left atrial structure and function and clinical outcomes in the general population. EUR HEART J 2013, 34(4):278-285.
29. Essayagh B, Antoine C, Benfari G, Messika-Zeitoun D, Michelena H, Le Tourneau T, Mankad S, Tribouilloy CM, Thapa P, Enriquez-Sarano M: Prognostic Implications of Left Atrial Enlargement in Degenerative Mitral Regurgitation. J AM COLL CARDIOL 2019, 74(7):858-870.
30. Leung M, van Rosendael PJ, Abou R, Ajmone MN, Leung DY, Delgado V, Bax JJ: Left atrial function to identify patients with atrial fibrillation at high risk of stroke: new insights from a large registry. EUR HEART J 2018, 39(16):1416-1425.
31. Park JJ, Park JH, Hwang IC, Park JB, Cho GY, Marwick TH: Left Atrial Strain as a Predictor of New-Onset Atrial Fibrillation in Patients With Heart Failure. JACC Cardiovasc Imaging 2020, 13(10):2071-2081.
32. Miyoshi H, Oishi Y, Mizuguchi Y, Iuchi A, Nagase N, Ara N, Oki T: Early predictors of alterations in left atrial structure and function related to left ventricular dysfunction in asymptomatic patients with hypertension. J AM SOC HYPERTENS 2013, 7(3):206-215.
33. Xu TY, Sun JP, Lee AP, Yang XS, Ji L, Zhang Z, Li Y, Yu CM, Wang JG: Left atrial function as assessed by speckle-tracking echocardiography in hypertension. Medicine (Baltimore) 2015, 94(6) :e526.
34. Onishi N, Kawasaki M, Tanaka R, Sato H, Saeki M, Nagaya M, Sato N, Minatoguchi S, Watanabe T, Ono K et al: Comparison between left atrial features in well-controlled hypertensive patients and normal subjects assessed by three-dimensional speckle tracking echocardiography. J CARDIOL 2014, 63(4):291-295.
35. Erol MK, Yilmaz M, Acikel M, Karakelleoglu S: Left atrial mechanical function in patients with essential hypertension. ACTA CARDIOL 2002, 57(5):323-327.
36. Yasuda R, Murata M, Roberts R, Tokuda H, Minakata Y, Suzuki K, Tsuruta H, Kimura T, Nishiyama N, Fukumoto K et al: Left atrial strain is a powerful predictor of atrial fibrillation recurrence after catheter ablation: study of a heterogeneous population with sinus rhythm or atrial fibrillation. Eur Heart J Cardiovasc Imaging 2015, 16(9):1008-1014.
37. Santos AB, Kraigher-Krainer E, Gupta DK, Claggett B, Zile MR, Pieske B, Voors AA, Lefkowitz M, Bransford T, Shi V et al: Impaired left atrial function in heart failure with preserved ejection fraction. EUR J HEART FAIL 2014, 16(10):1096-1103.
38. Melenovsky V, Hwang SJ, Redfield MM, Zakeri R, Lin G, Borlaug BA: Left atrial remodeling and function in advanced heart failure with preserved or reduced ejection fraction. Circ Heart Fail 2015, 8(2):295-303.
39. Sugimoto T, Bandera F, Generati G, Alfonzetti E, Bussadori C, Guazzi M: Left Atrial Function Dynamics During Exercise in Heart Failure: Pathophysiological Implications on the Right Heart and Exercise Ventilation Inefficiency. JACC Cardiovasc Imaging 2017, 10(10 Pt B):1253-1264.