Skip to main content
SpringerLink
Log in

Left Atrial Remodeling Mechanisms Associated with Atrial Fibrillation

  • Review
  • Published:
Cardiovascular Engineering and Technology Aims and scope Submit manuscript

Abstract

Heart disease has always been one of the important diseases that endanger health and cause death. Therefore, it is particularly important to understand left atrium reconstruction and atrial fibrillation before heart image processing. The purpose of this paper is to provide an important review of the mechanisms of left atrial remodeling (LAR) associated with atrial fibrillation (AF). LAR refers to the spectrum of pathophysiological changes in (i) atrial structure and physiological function, and (ii) electric, ionic, and molecular milieu of the LA, in response to stresses imposed by conditions such as hypertension, myocardial ischemia, autonomic denervation and congestive heart failure. The main mechanisms of LAR include electrical remodeling, structural remodeling, metabolic remodeling, autonomic remodeling, neurohormones and inflammation, and other influencing factors. LAR is not only the basic mechanism of AF and heart failure, but also the pathophysiological basis of its progression. In clinical practice, AF is the most common persistent arrhythmia, and is believed to be the result of a combination of mechanisms that have triggers and maintenance mechanisms, including spontaneous ectopic pacing and multiple wavelet reentry. While LA electrophysiological, structural, and ultra-structural changes trigger AF, in turn, AF alters the LA electrical and structural properties that promote its maintenance and recurrence. Chronic AF leads to extensive changes in atrial cellular substructures, including loss of myofibrils, accumulation of glycogen, changes in mitochondrial shape and size, fragmentation of sarcoplasmic reticulum, and dispersion of nuclear chromatin. Electrical remodeling and structural remodeling of the atria during AF, involving structural changes and functional impairment of the left atrium, can lead to serious decline in left ventricular function and severe heart failure. Therefore, LAR and AF are inter-activating phenomena, and the resulting complications can cause serious disabling and fatal events. In this paper, we present (i) the mechanisms of LAR, in the form of structural, electrical, metabolic, and neurohormonal changes, and (ii) their interactive roles in initiating and maintaining AF. These in-depth understanding of the atrial remodeling mechanisms can in turn provide useful insights into the treatment of AF and heart failure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Akoum, N., M. Daccarett, C. McGann, 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. 22(1):16–22, 2011.

    Google Scholar 

  2. Arindam, B., A. Adel, C. Himadri, et al. Three dimensional numerical analysis of hemodynamic of stenosed artery considering realistic outlet boundary conditions. Comput. Methods Programs Biomed. 2019. https://doi.org/10.1016/j.cmpb.2019.105163.

    Article  Google Scholar 

  3. Azevedo, P. S., M. F. Minicucci, P. P. Santos, et al. Energy metabolism in cardiac remodeling and heart failure. Cardiol. Rev. 21(3):135–140, 2013.

    Google Scholar 

  4. Barth, A. S., and G. F. Tomaselli. Cardiac metabolism and arrhythmias. Circulation 2(3):327–335, 2009.

    Google Scholar 

  5. Baum, J., and H. S. Duffy. Fibroblasts and myofibroblasts: what are we talking about? J. Cardiovasc. Pharmacol. 57(4):376–379, 2011.

    Google Scholar 

  6. Boersma, L. V., M. Castella, B. W. Van, et al. Atrial fibrillation catheter ablation versus surgical ablation treatment (FAST) a 2-center randomized clinical trial. South China J. Cardiol. 125(1):23, 2012.

    Google Scholar 

  7. Cha, Y. M., P. P. Dzeja, W. K. Shen, et al. Failing atrial myocardium: energetic deficits accompany structural remodeling and electrical instability. Am. J. Physiol. 284(4):H1313–H1320, 2003.

    Google Scholar 

  8. Cheng, C., D. Tempel, R. van Haperen, et al. Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 113:2744–2753, 2006.

    Google Scholar 

  9. Chrysostomakis, S. I., I. K. Karalis, E. N. Simantirakis, et al. Angiotensin II type 1 receptor inhibition is associated with reduced tachyarrhythmia-induced ventricular interstitial fibrosis in a goat atrial fibrillation model. Cardiovasc. Drugs Ther. 21(5):357–365, 2007.

    Google Scholar 

  10. Cuhlmann, S., K. Van der Heiden, D. Saliba, et al. Disturbed Blood Flow Induces RelA Expression via c-Jun N-Terminal Kinase 1: A Novel Mode of NF- kB Regulation That Promotes Arterial Inflammation. Circ. Res. 108:950–959, 2011.

    Google Scholar 

  11. Da, Z., W. Zhong, R. J. Van der Geest, et al. Accuracy of late gadolinium enhancement - magnetic resonance imaging in the measurement of left atrial substrate remodeling in patients with rheumatic mitral valve disease and persistent atrial fibrillation. Int. Heart J. 56(5):505–510, 2015.

    Google Scholar 

  12. Dawson, K., R. Wakili, B. Ordog, et al. MicroRNA29: a mechanistic contributor and potential biomarker in atrial fibrillation. Circulation 127(14):1466–1475, 2013.

    Google Scholar 

  13. Doenst, T., and E. D. Abel. Spotlight on metabolic remodeling is heart failure. Cardiovasc. Res. 90:191–193, 2011.

    Google Scholar 

  14. Doenst, T., G. Pytel, A. Schrepper, et al. Decreased rates of substrate oxidation ex vivo predict the onset of heart failure and contractile dysfunction in rats with pressure overload. Cardiovasc. Res. 86(3):461–470, 2010.

    Google Scholar 

  15. Dyverfeldt, P., M. D. Hope, E. E. Tseng, et al. Magnetic resonance measurement of turbulent kinetic energy for the estimation of irreversible pressure loss in aortic stenosis. JACC 6(1):64–71, 2013.

    Google Scholar 

  16. François, C. J., S. Srinivasan, M. L. Schiebler, et al. 4D cardiovascular magnetic resonance velocity mapping of alterations of right heart flow patterns and main pulmonary artery hemodynamics in tetralogy of Fallot. J. Cardiovasc. Magn. Reson. 14:16, 2012.

    Google Scholar 

  17. Fuchs, T., E. L. Baron, M. Leitman, et al. Does chronic atrial fibrillation induce cardiac remodeling? Echocardiography 30(2):140–146, 2013.

    Google Scholar 

  18. Fyrenius, A., L. Wigström, T. Ebbers, et al. Three dimensional flow in the human left atrium. Heart 86:448–455, 2001.

    Google Scholar 

  19. Gardner, J. D., D. B. Murray, T. G. Voloshenyuk, et al. Estrogen attenuates chronic volume overload induced structural and functional remodeling in male rat hearts. AJP 298(2):H497–H504, 2010.

    Google Scholar 

  20. Han, F. T., N. Akoum, and N. Marrouche. Value of magnetic resonance imaging in guiding atrial fibrillation management. Can. J. Cardiol. 29(10):1194–1202, 2013.

    Google Scholar 

  21. Han, F. T., and N. Marrouche. An atrial fibrosis-based approach for atrial fibrillation ablation. Future Cardiol. 11(6):673–681, 2015.

    Google Scholar 

  22. Heijman, J., N. Voigt, S. Nattel, et al. Cellular and molecular electrophysiology of atrial fibrillation initiation, maintenance, and progression. Circ. Res. 114(9):1483–1499, 2014.

    Google Scholar 

  23. Hoit, B. D. Left atrial size and function: role in prognosis. J. Am. Coll. Cardiol. 63(6):493–505, 2014.

    Google Scholar 

  24. Hwang, H. J., J. W. Ha, B. Joung, et al. Relation of inflammation and left atrial remodeling in atrial fibrillation occurring in early phase of acute myocardial infarction. Int. J. Cardiol. 146(1):0–31, 2011.

    Google Scholar 

  25. Iwasaki, Y. K., K. Nishida, T. Kato, et al. Atrial fibrillation pathophysiology implications for management. Circulation 124(20):2264–2274, 2011.

    Google Scholar 

  26. Jalali, M., H. Behnam, F. Davoodi, and M. Shojaeifard. Temporal super-resolution of 2D/3D echocardiography using cubic B-spline interpolation. Biomed. Signal Process. Control 1(58):101868, 2020.

    Google Scholar 

  27. Jalife, J., and K. Kaur. Atrial remodeling, fibrosis, and atrial fibrillation. Trends Cardiovasc. Med. 25(6):475–484, 2015.

    Google Scholar 

  28. Jayachandran, J. V., H. J. Sih, W. Winkle, et al. Atrial fibrillation produced by prolonged rapid atrial pacing is associated with heterogeneous changes in atrial sympathetic innervation. Circulation 101(10):1185–1191, 2000.

    Google Scholar 

  29. Khan, A., G. W. Moe, N. Nili, et al. The cardiac atria are chambers of active remodeling and dynamic collagen turnover during evolving heart failure. J. Am. Coll. Cardiol. 43(1):68–76, 2004.

    Google Scholar 

  30. Kim, Y. G., J. Shim, S. K. Oh, et al. Different responses of left atrium and left atrial appendage to radiofrequency catheter ablation of atrial fibrillation: a follow up MRI study. Sci. Rep. 8(1):7871, 2018.

    Google Scholar 

  31. Klein, C., J. Brunereau, D. Lacroix, et al. Left atrial epicardial adipose tissue radiodensity is associated with electrophysiological properties of atrial myocardium in patients with atrial fibrillation. Eur. Radiol. 29(6):3027–3035, 2018.

    Google Scholar 

  32. Krittian, S. B., P. Lamata, C. Michler, et al. A finite-element approach to the direct computation of relative cardiovascular pressure from time-resolved MR velocity data. Med. Image Anal. 16:1029–1037, 2012.

    Google Scholar 

  33. Lacalzada-Almeida, J., M. M. Izquierdo-Gómez, C. Belleyo-Belkasem, et al. Interatrial block, and atrial remodeling assessed using speckle tracking echocardiography. BMC Cardiovas. Disord. 18(1):38, 2018.

    Google Scholar 

  34. Lau, C. P., H. F. Tse, C. W. Siu, et al. Atrial electrical and structural remodeling: implications for racial differences in atrial fibrillation. J. Cardiovasc. Electrophysiol. 23(s1):s36–s40, 2012.

    Google Scholar 

  35. Leung, D. Y., A. Boyd, A. A. Ng, et al. Echocardiographic evaluation of left atrial size and function: current understanding, pathophysiologic correlates, and prognostic implications. Am. Heart J. 156(6):0-1064, 2008.

    Google Scholar 

  36. Li, Y., Y. B. Deng, X. J. Bi, Y. N. Liu, J. Zhang, and L. Li. Evaluation of myocardial strain and artery elasticity using speckle tracking echocardiography and high-resolution ultrasound in patients with bicuspid aortic valve. Int. J. Cardiovasc. Imaging 32(7):1063–1069, 2016.

    Google Scholar 

  37. Li, Y. Y., C. F. McTiernan, and A. M. Feldman. Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovasc. Res. 46(2):214–224, 2000.

    Google Scholar 

  38. Markl, M., M. T. Draney, M. D. Hope, et al. Time-resolved 3-dimensional velocity mapping in the thoracic aorta: visualization of 3-directional blood flow patterns in healthy volunteers and patients. J. Comput. Assist. Tomogr. 28:459–468, 2004.

    Google Scholar 

  39. Marrouche, N. F., D. Wilber, G. Hindricks, et al. Association of atrial tissue fibrosis identified by delayed enhancement MRI and atrial fibrillation catheter ablation: the DECAAF study. JAMA 311(5):498–506, 2014.

    Google Scholar 

  40. Masamichi, H. M. D., D. C. M. D. Mark, and R. L. P. D. Kenneth. Cellular mechanisms of vagally mediated atrial tachyarrhythmia in isolated arterially perfused canine right atria. J. Cardiovasc. Electrophysiol. 13(9):918–926, 2010.

    Google Scholar 

  41. Mclarty, J. L., J. Li, S. P. Levick, et al. Estrogen modulates the influence of cardiac inflammatory cells on function of cardiac fibroblasts. J. Inflamm. Res. 6(default):99–108, 2013.

    Google Scholar 

  42. Nattle, S. Electrophysiologic remodeling: are ion channels static players or dynamic movers? J. Cardiovasc. Electrophysiol. 10:1553–1556, 1999.

    Google Scholar 

  43. Ng, J., R. Villuendas, I. Cokic, et al. Autonomic remodeling in the left atrium and pulmonary veins in heart failure: creation of a dynamic substrate for atrial fibrillation. Circulation 4(3):388–396, 2011.

    Google Scholar 

  44. Okumura Y. Inflammatory biomarkers in atrial fibrillation: are they linked to future outcomes? Heart, 2016.

  45. Oliver, W., G. Matthews, C. R. Ayers, et al. Factors associated with left atrial remodeling in the general populationCLINICAL PERSPECTIVE. Circulation 10(2):e005047, 2017.

    Google Scholar 

  46. Platonov, P. G., L. B. Mitrofanova, V. Orshanskaya, et al. Structural abnormalities in atrial walls are associated with presence and persistency of atrial fibrillation but not with age. J. Am. Coll. Cardiol. 58(21):2225–2232.9, 2011.

    Google Scholar 

  47. Roberta, A., C. P. Salvatore, C. Pio, et al. Left atrium by echocardiography in clinical practice: from conventional methods to new echocardiographic techniques. Sci. World J. 2014. https://doi.org/10.1155/2014/451042.

    Article  Google Scholar 

  48. Rossi, A., M. Gheorghiade, F. Triposkiadis, et al. Left atrium in heart failure with preserved ejection fraction: structure, function, and Significance. Circ. Heart Failure 7(6):1042–1049, 2014.

    Google Scholar 

  49. Saha S, Islam M, Rahimi-Gorji M, et al. Aerosol particle transport and deposition in a CT-scan based mouth-throat model. Computer Methods and Programs in Biomedicine, Vol 180, 2019, 105010, AIP Conference Proceedings 2121, 040011,

  50. Schoonderwoerd, B. A., I. C. V. Gelder, D. J. V. Veldhuisen, et al. Electrical and structural remodeling: role in the genesis and maintenance of atrial fibrillation. Prog. Cardiovasc. Dis. 48(3):153–168, 2005.

    Google Scholar 

  51. Schotten, U. Electrical and contractile remodeling during the first days of atrial fibrillation go hand in hand. Circulation 107(10):1433–1439, 2003.

    Google Scholar 

  52. Shanshan, Z., S. Wanqing, Z. Zhiguo, et al. The role of Nrf2-mediated pathway in cardiac remodeling and heart failure. Oxid. Med. Cell. Long. 2014:1–16, 2014.

    Google Scholar 

  53. Shao, X. D., L. Jun, J. L. Wei, et al. Can atrial myoelectric remodeling promote atrial fibrillation? Med. Contend 5(2):140–146, 2014.

    Google Scholar 

  54. Shao-Hua, Z., Z. Yu-Jiao, L. I. Zhi-Yuan, et al. Autonomic neural remodeling of pulmonary vein-left atrium junction in a prolonged right atrial pacing canine model. J. Shandong Univ. (Health Sciences) 37(6):745–750, 2013.

    Google Scholar 

  55. Sharif, H., L. Wainman, D. O’Leary, et al. The effect of blood volume and volume loading on left ventricular diastolic function in individuals with spinal cord injury. Spinal Cord 55(8):753–758, 2017.

    Google Scholar 

  56. Srivastava, U., A. Bhattacharya, M. Boutjdir, et al. Mechanisms of atrial electrical remodeling in obese heart. Biophys. J . 114(3):383a, 2018.

    Google Scholar 

  57. Thomas, L., and W. P. Abhayaratna. Left atrial reverse remodeling: mechanisms, evaluation, and clinical significance. Jacc Cardiovasc. Imaging 10(1):65, 2017.

    Google Scholar 

  58. Tuunanen, H., and J. Knuuti. Metabolic remodelling in human heart failure. Cardiovasc. Res. 90(2):251–257, 2011.

    Google Scholar 

  59. Tzima, E., M. Irani-Tehrani, W. B. Kiosses, et al. A mechanosensory complex that mediates the endothelial cell response to fluid shear stress. Nature 437:426–431, 2005.

    Google Scholar 

  60. Vanbilsen, M., P. Smeets, A. Gilde, et al. Metabolic remodelling of the failing heart: the cardiac burn-out syndrome? Cardiovasc. Res. 61(2):218–226, 2004.

    Google Scholar 

  61. Wang, W., H. T. Zhang, and X. L. Yang. Effect of matrix metalloproteinase and their inhibitors on atrial myocardial structural remodeling. J. Cardiovasc. Med. 14(4):265–269, 2013.

    Google Scholar 

  62. Westermann, D., D. Lindner, M. Kasner, et al. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ. Heart Fail 4(1):44–52.15, 2011.

    Google Scholar 

  63. Wijffels, M. C. E. F., C. J. H. J. Kirchhof, R. Dorland, et al. Atrial fibrillation begets atrial fibrillation: a study in awake chronically instrumented goats. Circulation 92(7):1954–1968, 1995.

    Google Scholar 

  64. Xu, Y., D. Sharma, G. Li, et al. Atrial remodeling: New pathophysiological mechanism of atrial fibrillation. Medical Hypotheses 80(1):53–56.12, 2013.

    Google Scholar 

  65. Yu, L., B. J. Scherlag, Y. Sha, et al. Interactions between atrial electrical remodeling and autonomic remodeling: How to break the vicious cycle. Heart Rhythm. 9(5):804–809, 2012.

    Google Scholar 

  66. Zajac, J., J. Eriksson, P. Dyverfeldt, et al. Turbulent kinetic energy in normal and myopathic left ventricles. J. Magn. Reson. Imaging 41(4):1021–1029, 2015.

    Google Scholar 

  67. Zhang, Y., S. Zheng, Y. Geng, et al. MicroRNA profiling of atrial fibrillation in canines: MiR-206 modulates intrinsic cardiac autonomic nerve remodeling by regulating SOD1. PLoS ONE 10(3):e0122674, 2015.

    Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China [Grant numbers 81771927, and 81601462], and the data provided by the radiology department of West China Hospital of Sichuan University.

Competing interests

The authors declare no competing interests.

Consent for publication

All the authors have given consent for publication of this paper.

Author information

Authors and Affiliations

  1. School of Electrical and Electronic Engineering, The University of Adelaide, Adelaide, SA, 5005, Australia

    Defu Qiu & Kelvin K. L. Wong

  2. Department of Radiology, West China Hospital, Sichuan University, Chengdu, 610041, China

    Liqing Peng

  3. Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Dhanjoo N. Ghista & Kelvin K. L. Wong

  4. University 2020 Foundation, San Jose, CA, 95126, USA

    Dhanjoo N. Ghista

Authors
  1. Defu Qiu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Liqing Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dhanjoo N. Ghista
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kelvin K. L. Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

DFQ: collection, organizing, and review of the literature; KKLW: preparing the manuscript, and manuscript review and modification; DNG and LQP: manuscript review, modification, editing, and revision. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kelvin K. L. Wong.

Additional information

Associate Editor Jeff N. Rottman oversaw the review of this article.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Qiu, D., Peng, L., Ghista, D.N. et al. Left Atrial Remodeling Mechanisms Associated with Atrial Fibrillation. Cardiovasc Eng Tech 12, 361–372 (2021). https://doi.org/10.1007/s13239-021-00527-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13239-021-00527-w

Keywords

Search

Navigation