Atrial Dispersion Predicts Atrial Fibrillation in Mitral Stenosis: A Five-Year Follow-Up SpeckleTracking Echocardiography Study

Özkan Candan

Department of Cardiology, Uşak University Faculty of Medicine, Uşak, Türkiye

Keywords: Mitral valve stenosis; atrial fibrillation; 2D echocardiography

Abstract

Introduction: Atrial dispersion showing increased electrical heterogeneity may be associated with the occurence of atrial fibrillation (AF). In our study, it was aimed to investigate the effects of atrial dispersion evaluated by speckle tracking echocardiography on the occurence of AF on in patients with mild to moderate rheumatic mitral stenosis.

Patients and Methods: Sixty-two patients with rheumatic mitral stenosis with sinus rhythm, asymptomatic or NYHA 1 symptoms were included in the study. The time to peak atrial strain was measured for each segment by speckle tracking echocardiography in two and four-chamber views. Atrial dispersion was calculated by taking the standard deviation of time to peak strain in 12 left atrial segments. Echocardiographic and clinical parameters of the patients were compared according to the development of AF.

Results: During follow-up (mean follow-up duration, 49.9 ± 12.9 months), 19 patients (30%) developed AF. Compared to patients who did not develop AF at follow-up, patients with AF were older (46.8 ± 10.2 vs. 35.9 ± 12, p= 0.001), while mitral valve area (MVA) (1.38 ± 0.1 vs. ± 1.49 ± 0.18 vs. p= 0.02), PALS (13.7 ± 4 vs. 18.8 ± 5.5, p= 0.001) and PACS (6 ± 2.3 vs. 8.2 ± 3.8, p= 0.002) were found to be lower. Atrial dispersion was found to be increased in patients who developed AF (63.2 ± 13.5 vs. 46.1 ± 22.3, p= 0.003). Age, atrial dispersion and PALS were determined as independent predictors of AF development in Cox regression analysis.

Conclusion: Atrial dispersion, a new parameter measured by STE, predicts the development of AF. Increased atrial dispersion may provide additional benefits in initiating prophylactic antiarrhythmic drug therapy or anticoagulants.

Introduction

Rheumatic heart disease affects the mitral valves and causes mitral stenosis very frequently. Despite advances, morbidity causes such as peripheral and cerebral embolic events, pulmonary edema, and deterioration in quality of life are still high(1,2). The frequency of atrial fibrillation (AF) in mitral stenosis has been found to be 30-50%(3). In mitral stenosis, increased atrial pressure causes inflammation and interstitial fibrosis in the atrial wall, leading to a decrease in atrial wall elasticity. The structural remodeling process leads to electrical remodeling and causes AF(4). Many clinical, echocardiographic and biochemical variables that cause AF in patients with mitral stenosis have been investigated(5-7). Two-dimensional (2D) strain imaging as assessed by speckle tracking echocardiography (STE) has been developed to examine both ventricular and atrial myocardial function(8-11).

Atrial dispersion with electrical heterogeneity has been found to be associated with occurence of AF in the normal population(12-14). In patients with reduced atrial dispersion, recurrence of AF was reduced after successful ablation(15).

In this study, it was aimed to investigate whether atrial strain and atrial dispersion used together with clinical parameters are associated with occurence of AF.

Materials and Methods

One hundred and twenty patients with mild or moderate rheumatic mitral stenosis were screened. Inclusion criteria were determined as patients with mild or moderate rheumatic mitral stenosis, asymptomatic patients and patients with EF> 65%, and 82 patients meeting the inclusion criteria were included in the study.

Exlucia criteria was described as anemia, chronic obstrictive pulmonary disease, hypertension, history of coronary artery intervention, NYHA class II-IV, modorate or severe aortic or mitral or tricuspid insufficiency. Eleven patients who did not come to the follow-up appointment and nine patients with inapropiate echocardiographic images were excluded from the study.

A 12-lead ECG was taken at each examination, and cardiac symptoms were evaluated. A rhythm Holter recording was done when the patient had symptoms suggestive of AF. AF was determined as rhythm without p waves and irregular RR intervals in 12 lead ECG(16).

Classic 2D-Echocardiography

All echocardiographic images were gathered by a Vivid 7 machine using a 3.5 MHz transducer. The acquired images were analyzed offline with the EchoPAC program. Data of classic 2D echocardiography and dopplers measurements were collected in accordance with the guidelines(17-20).

Speckle Tracking Echocardiography

Apical 2 and 4 chambers view has been used to evaluate left atrail strain. The narrowest volume of left atrial endocardium was marked manually. Additional lines were created automatically in the epicardial and middle myocardial regions with the software. Before the analysis, it was checked whether the line formed was visually appropriate for endocardial follow-up. If not appropriate, it was corrected again manually. Left atrial endocardium was divided into six segments.

Peak atrial longitudinal stretch (PALS) was defined as the strain in the left atrium reaching its largest volume while (PACS) was defined as the strain immediately after the p wave in the ECG. In total, strain analysis was performed on 744 segments, and 3.9% of the segments were not included in the study.

Time from the onset of the QRS complex to the peak strain was calculated for each left atrial wall segment. Standard deviation of the electrical delay of a total of 12 segments was calculated and defined as the atrial dispersion(14).

Our study adhered to the Helsinki Declaration, and all patients provided written informed consent. The Ethics Committee of Kartal Koşuyolu High Specialization Training and Research Hospital approved the study in İstanbul, Türkiye.

Statistical Analysis

In the analysis of continuous variables between the two groups, Student’s t test or Mann-Whitney U test was used, depending on whether it showed normal distribution or not. χ2 or Fisher’s exact test was used for categorical variables, and Pearson’s correlation test was used for correlation analysis. Cox regression testing was used to identify predictors contributing to the development of AF. Variables that were significant in a single analysis were used to perform multivariate analysis. For statistical significance, p value was determined as <0.05 and SPSS (version 24.0) program was used.

Results

Sixty-two patients with isolated mild-to-moderate mitral stenosis (40% male, mean age 39.2 ± 12.5 years) were included in the study. Clinical features and echocardiographic data of the study patients are shown in Table 1.

Table 1. Echocardiographic and clinical characteristic of the study population

Atrial fibrillation was detected in 19 patients (30%) during the follow-up period (mean follow-up= 49.9 ± 12.9 months). Eight of these patients had paroxysmal and 11 had persistent AF. Patients who developed AF were older than those who did not (46.8 ± 10.2 vs. 35.9 ± 12, p= 0.001). MVA (PLN) (1.38 ± 0.15 vs. 1.49 ± 0.18, p= 0.025) and global PALS (%) (13.7 ± 4 vs. 18.8 ± 5.5, p≤ 0.001) and global PACS (%) (6 ± 2.3 vs. 8.2 ± 3.8, p= 0.008) were statistically significantly lower in patients who developed AF (Table 1) (Figure 1).

Figure 1. Left atrial longitudinal strain parameters. PALS: Peak atrial longitudinal strain, PACS: Peak atrial contraction strain.

Atrial dispersion was found to be statistically significantly prolonged in patients with AF (63.2 ± 13.5 vs. 46.1 ± 22.3 p= 0.001) (Table 1) (Figures 2, 3). However, the relation between atrial dispersion and AF type (permanent or paroxysmal) could not be determined (60.8 ± 7.5 ms vs. 66.4 ± 19.2, p= 0.45). There was no significant difference between the two groups in terms of left atrial diameter, left atrial volume index, and pulmonary artery systolic pressure (Table 1).

Figure 2. Speckle-based left atrial dispersion of with atrial fibrillation. AD: Atrial dispersion.

Figure 3. Speckle-based left atrial dispersion of without atrial fibrillation. AD: Atrial dispersion.

No significant correlation was observed between atrial dispersion (ms) and age (years), left atrial diameter (cm), left atrial volume index (mL/m2 ), PALS (%), PACS (%), MVA PHT, maximum gradient and mean gradient. Only a moderate correlation was observed between atrial dispersion and MVA measured by the planimetric method (r= -0.38, p= 0.002).

Multivariate regression analysis was used to identify predictors of the development of AF. Atrial dispersion, PALS, age, and MVA (PLN), which were significant in the univariate analysis, were included in regression analysis. Atrial dispersion (ms) (HR= 1.033, 95 CI= 1.009-1.059, p= 0.008), age (years) (HR= 1.045, 95% CI= 1.001-1.091, p= 0.047) and PALS (HR= 0.868, 95%) (CI= 0.783-0.963, p= 0.007) were identified as independent predictors for the development of AF (Table 3).

Table 2. Correlation of atrial dispersion

Table 3. The results of cox regression analysis for the prediction of atrial fibrillation

Discussion

Decreased PALS and greater atrial dispersion are associated with the occurence of AF in mitral stenosis.

Pressure increase in mitral stenosis causes an increase in interstitial fibrosis and contributes to the deterioration of atrial relaxation. As a result, the reservoir functions of the left atrium are impaired. Thus, electrical remodeling including shortening of the atrial effective refractory period and increased refractory period distribution may lead to the development of AF(21,22).

PALS is used in the evaluation of reservoir function(9,10). Decreased PALS may indicate impaired dilatation capacity (reservoir function) of the atrial tissue and may be useful in differentiating patients who may develop AF. PALS has been shown to be associated with the development of AF after cardiac surgery(23-25). In addition to other echocardiographic and clinical parameters, LA strain has been found to be more accurate in predicting the development of AF in patients with mitral stenosis at follow up(26,27). Similar to previous studies, in our study, global PALS was found to be predictive of the development of AF. Decreased PALS indicates impaired atrial reservoir function and thus, susceptibility to the development of AF.

Various diseases leading to fibrosis in the left ventricle and left atrium cause electrical asynchrony or dispersion by creating foci whose electrical stimulation occurs at different times. Subsequently, mechanical asynchrony may occur, triggering the formation of arrhythmia. Although atrial dispersion can be evaluated by various echocardiographic methods, it is more accurately and easily evaluated with speckle tracking echocardiography.

In a study of normal subjects predisposed to develop heart failure and AF, atrial dispersion has been found to be associated with the occurence of AF(28). Atrial dispersion has been found to be associated with the occurence of recurrence in patients undergoing ablation for paroxysmal AF, and another study has found that prolonged atrial dispersion is significantly reduced after successful DC cardioversion in patients undergoing DC cardioversion in this patient group(15,29). In a study by Kupczynska et al., increased atrial dispersion has been associated with the formation of thrombus in the atrial appendage(30). In our study, atrial dispersion is associated with the development of AF. In patients with mitral stenosis, electrical heterogeneity in the atrial wall causes irregularities in conduction velocities and refractory periods. The resulting electrical remodeling can lead to electromechanical dysfunction and consequent development of AF(4). According to the most recent ESC valvular diseases guideline, new onset AF contributes to the timing of decision for percutaneous mitral balloon valvuloplasty or surgical intervention in asymptomatic patients with mitral stenosis. Since atrial dispersion is also associated with AF in this patient group, it can be used to decide the time of intervention(31).

In this study, age was found to be associated with the occurence of AF. With increasing age, fibrosis in the atrial tissue increases more and leads to the development of AF(26).

Conclusion

Atrial dispersion as assessed by STE is associated with the development of AF. Atrial dispersion may provide additional information for the early initiation of antiarrhythmic drug therapy or anticoagulant therapy.

Limitations

The significant limitation is the study was that it was single-centered and the number of patients was relatively small. Since we did not have a special software for atrial strain assessment, the software used for ventricular strain assessment was utilized. Again, speckle tracking echocardiography evaluation was excluded from the analysis in some patients due to the requirement for good image quality. The frequency of AF may have been seen to be underestimated since the methods we used for detecting AF could not particularly detect patients with asymptomatic AF.

Cite this article as: Candan Ö. Atrial dispersion predicts atrial fibrillation in mitral stenosis: A five-year follow-up speckle-tracking echocardiography study Koşuyolu Heart J 2023;26(1):27-33.

Ethics Committee Approval

This study was approved by Kartal Koşuyolu High Specialization Training and Research Clinical Research Ethics Committee (Decision no: 20/7/7/39, Date: 21.09.2017).

Peer Review

Externally peer-reviewed.

Author Contributions

Concept/Design - ÖC; Analysis/Interpretation - ÖC; Data Collection - ÖC; Writing - ÖC; Critical Revision - AK; Final Approval - ÖC; Statistical Analysis - ÖC; Overall Responsibility - ÖC.

Conflict of Interest

The author have no conflicts of interest to declare.

Financial Disclosure

The author declare that this study has received no financial support.

References

  1. Chandrashekhar Y, Westaby S, Narula J. Mitral stenosis. Lancet 2009;374(9697):1271-83. [Crossref] DOI: 10.1016/S0140-6736(09)60994-6
  2. Chugh SS, Blackshear JL, Shen WK, Hammill SC, Gersh BJ. Epidemiology and natural history of atrial fibrillation: Clinical implications. J Am Coll Cardiol 2001;37(2):371-8. [Crossref] DOI: 10.1016/S0735-1097(00)01107-4
  3. Otto CM, Nishimura RA, Bonow RO, Carabello BA, Erwin JP 3rd, Gentile F, et al. 2020 ACC/AHA guideline for the management of patients with valvular heart disease: Executive summary: A report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. J Am Coll Cardiol 2021;77(4):450-500. [Crossref] DOI: 10.1161/CIR.0000000000000932
  4. Josephson ME, Kastor JA, Morganroth J. Electrocardiographic left atrial enlargement. Electrophysiologic, echocardiographic and hemodynamic correlates. Am J Cardiol 1977;39(7):967-71. [Crossref] DOI: 10.1016/S0002-9149(77)80209-9
  5. Kim HJ, Cho GY, Kim YJ, Kim HK, Lee SP, Kim HL, et al. Development of atrial fibrillation in patients with rheumatic mitral valve disease in sinus rhythm. Int J Cardiovasc Imaging 2015;31(4):735-42. [Crossref] DOI: 10.1007/s10554-015-0613-2
  6. Krishnamoorthy KM, Dash PK. Prediction of atrial fibrillation in patients with severe mitral stenosis-role of atrial contribution to ventricular filling. Scand Cardiovasc J 2003;37(6):344-8. [Crossref] DOI: 10.1080/14017430310015893
  7. Ozaydin M, Turker Y, Varol E, Alaca S, Erdogan D, Yilmaz N, et al. Factors associated with the development of atrial fibrillation in patients with rheumatic mitral stenosis. Int J Cardiovasc Imaging 2010;26(5):547-52. [Crossref] DOI: 10.1007/s10554-010-9609-0
  8. Karabay CY, Zehir R, Güler A, Oduncu V, Kalayci A, Aung SM, et al. Left atrial deformation parameters predict left atrial appendage function and thrombus in patients in sinus rhythm with suspected cardioembolic stroke: A speckle tracking and transesophageal echocardiography study. Echocardiography 2013;30(5):572-81. [Crossref] DOI: 10.1111/echo.12089
  9. Okamatsu K, Takeuchi M, Nakai H, Nishikage T, Salgo IS, Husson S, et al. Effects of aging on left atrial function assessed by two-dimensional speckle tracking echocardiography. J Am Soc Echocardiogr 2009;22(1):70-5. [Crossref] DOI: 10.1016/j.echo.2008.11.006
  10. Vianna-Pinton R, Moreno CA, Baxter CM, Lee KS, Tsang TSM, Appleton CP. Two-dimensional speckle-tracking echocardiography of the left atrium: Feasibility and regional contraction and relaxation differences in normal subjects. J Am Soc Echocardiogr 2009;22(3):299-305. [Crossref] DOI: 10.1016/j.echo.2008.12.017
  11. Saraiva RM, Demirkol S, Buakhamsri A, Greenberg N, Popović ZB, Thomas JD, et 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):172-80. [Crossref] DOI: 10.1016/j.echo.2009.11.003
  12. Candan O, Gecmen C, Kahyaoğlu M, Şimsek Z, Çelik M, Uslu A, et al. Clinical utility of left atrial asynchrony and mechanical function in patients with hypertrophic cardiomyopathy. Acta Cardiol Sin 2022;38(2):141-50.
  13. Shang Z, Su D, Cong T, Sun Y, Liu Y, Chen N, et al. Assessment of left atrial mechanical function and synchrony in paroxysmal atrial fibrillation with two-dimensional speckle tracking echocardiography. Echocardiography (Mount Kisco, NY). 2017;34(2):176-83. [Crossref] DOI: 10.1111/echo.13434
  14. Kawakami H, Ramkumar S, Nolan M, Wright L, Yang H, Negishi K, et al. Left atrial mechanical dispersion assessed by strain echocardiography as an independent predictor of new-onset atrial fibrillation: A case-control study. J Am Soc Echocardiogr 2019;32(10):1268-76.e3. [Crossref]
  15. Sarvari SI, Haugaa KH, Stokke TM, Ansari HZ, Leren IS, Hegbom F, et al. Strain echocardiographic assessment of left atrial function predicts recurrence of atrial fibrillation. Eur Heart J Cardiovasc Imaging 2016;17(6):660-7. [Crossref] DOI: 10.1093/ehjci/jev185
  16. Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomström-Lundqvist C, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2021;42(5):373- 498. [Crossref] DOI: 10.1093/eurheartj/ehaa945
  17. Baumgartner H, Hung J, Bermejo J, Chambers JB, Evangelista A, Griffin BP, et al. Echocardiographic assessment of valve stenosis: EAE/ASE recommendations for clinical practice. Eur J Echocardiogr 2009;10(1):1- 25. [Crossref] DOI: 10.1093/ejechocard/jen303
  18. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, 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):233-70. [Crossref] DOI: 10.1093/ehjci/jev014
  19. Schabelman S, Schiller NB, Silverman NH, Ports TA. Left atrial volume estimation by two-dimensional echocardiography. Cathet Cardiovasc Diagn 1981;7(2):165-78. [Crossref] DOI: 10.1002/ccd.1810070206
  20. Pepi M, Tamborini G, Galli C, Barbier P, Doria E, Berti M, et al. A new formula for echo-Doppler estimation of right ventricular systolic pressure. J Am Soc Echocardiogr 1994;7(1):20-6. [Crossref] DOI: 10.1016/S0894-7317(14)80414-8
  21. Jaïs P, Peng JT, Shah DC, Garrigue S, Hocini M, Yamane T, et al. Left ventricular diastolic dysfunction in patients with so-called lone atrial fibrillation. J Cardiovasc Electrophysiol 2000;11(6):623-5. [Crossref] DOI: 10.1111/j.1540-8167.2000.tb00023.x
  22. Satoh T, Zipes DP. Unequal atrial stretch in dogs increases dispersion of refractoriness conducive to developing atrial fibrillation. J Cardiovasc Electrophysiol 1996;7(9):833-42. [Crossref] DOI: 10.1111/j.1540-8167.1996.tb00596.x
  23. Cameli M, Lisi M, Reccia R, Bennati E, Malandrino A, Solari M, et al. Pre-operative left atrial strain predicts post-operative atrial fibrillation in patients undergoing aortic valve replacement for aortic stenosis. Int J Cardiovasc Imaging 2014;30(2):279-86. [Crossref] DOI: 10.1007/s10554-013-0323-6
  24. Pham TD, Fenoglio JJJ. Right atrial ultrastructural in chronic rheumatic heart disease. Int J Cardiol 1982;1(3-4):289-304. [Crossref] DOI: 10.1016/0167-5273(82)90091-2
  25. Verdejo HE, Becerra E, Zalaquet R, Del Campo A, Garcia L, Troncoso R, et al. Atrial function assessed by speckle tracking echocardiography is a good predictor of postoperative atrial fibrillation in elderly patients. Echocardiography 2016;33(2):242-8. [Crossref] DOI: 10.1111/echo.13059
  26. Pourafkari L, Ghaffari S, Bancroft GR, Tajlil A, Nader ND. Factors associated with atrial fibrillation in rheumatic mitral stenosis. Asian Cardiovasc Thorac Ann 2015;23(1):17-23. [Crossref] DOI: 10.1177/0218492314530134
  27. Ancona R, Comenale Pinto S, Caso P, Di Salvo G, Severino S, D’Andrea A, et al. 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(3):270-7. [Crossref] DOI: 10.1016/j.echo.2012.11.016
  28. Kawakami H, Ramkumar S, Nolan M, Wright L, Yang H, Negishi K, et al. Left atrial mechanical dispersion assessed by strain echocardiography as an independent predictor of new-onset atrial fibrillation: A case-control study. J Am Soc Echocardiogr 2019;32(10):1268-76.e3. [Crossref] DOI: 10.1016/j.echo.2019.06.002
  29. Degiovanni A, Bortnik M, Dell’Era G, Bolzani V, Occhetta E, Bellomo G, et al. Analysis of electrical and mechanical left atrial properties in patients with persistent atrial fibrillation. Int J Cardiovasc Imaging 2013;29(1):71- 8. [Crossref] DOI: 10.1007/s10554-012-0053-1
  30. Kupczynska K, Michalski BW, Miskowiec D, Kasprzak JD, Szymczyk E, Wejner-Mik P, et al. Incremental value of left atrial mechanical dispersion over CHA2DS2-VASc score in predicting risk of thrombus formation. Echocardiography 2018;35(5):651-60. [Crossref] DOI: 10.1111/echo.13899
  31. Vahanian A, Beyersdorf F, Praz F, Milojevic M, Baldus S, Bauersachs J, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2022;43(7):561-632. [Crossref] DOI: 10.1093/ejcts/ezac209

Figure and Tables

Figure 1. Left atrial longitudinal strain parameters. PALS: Peak atrial longitudinal strain, PACS: Peak atrial contraction strain.
Figure 2. Speckle-based left atrial dispersion of with atrial fibrillation. AD: Atrial dispersion.
Figure 3. Speckle-based left atrial dispersion of without atrial fibrillation. AD: Atrial dispersion.
Table 1. Echocardiographic and clinical characteristic of the study population
Table 2. Correlation of atrial dispersion
Table 3. The results of cox regression analysis for the prediction of atrial fibrillation