Mechanisms of Arrhythmogenesis and Risk Factors for Thromboembolic Events in Patients with Atrial Fibrillation without Concomitant Coronary and Valvular Heart Disease

Cover Page
Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


Aims  identification the correlates between parameters of tissue Doppler imaging, EF thickness by MRI and biochemical markers of fibrosis and inflammation in patients with nonvalvular AF. Retrospectively to evaluate clinical and instrumental parameters influencing the development of thromboembolic events. Methods. Data analysis was performed on 151 patients with different type of AF. A retrospective analysis included 112 patients. 15 (13%) had a history of LAA thrombosis and/or thromboembolic events (stroke, TIA). The prospective analysis included 39 patients. We identified groups with idiopathic AF (N = 21), AF with arterial hypertension (N = 18). And also a group with normal or slightly enlarged (<4.5 sm) LA s (N = 29), and with LA ≥ 4.5 sm (N = 10). Echocardiography with tissue Doppler imaginе and cardiac MRI were performed. The level of: matrix metalloproteinases (MMP-2, MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), transforming growth factor beta-1 (TGF beta-1), soluble intercellular adhesion molecule (sICAM) was assessed. Results. The following parameters were significantly associated with LA thrombosis and thromboembolic events: age over 50 years (p = 0.001), obesity (p = 0.036), persistent AF (p = 0.003), the phenomenon of spontaneous ECHO contrast in LA (p = 0.03), the blood flow velocity in the LAA less than 30 sm / s (p = 0.005), morphological type III of LAA (p = 0.012). The greatest correlation between the thickness of the EFT and biomarkers was observed relative to: MMP-9 (τ  = 0.65; Tcr = 0.16), TIMP-1 (τ = 0.71; Tcr = 0.18) in the group of idiopathic AF; and TGF-beta1 (τ = 0.22; Tcr = 0.19) in the general group. The percentage of left atrial myocardial fibrosis was correlated with TIMP-1 levels. There was a correlation between E/e‘ and MMP-9, TIMP-1 in patients with idiopathic AF (τ = 0.65; Tcr = 0.16 and τ = 0.56; Tcr = 0.21 respectively). Conclusion. The increasing levels of MMP-9 and TIMP-1 are associated with epicardial fat thickness by MRI. In addition to CHA2DS2VASc scale, we identified novel predictors of LA thrombosis and/or thromboembolic events, which are: chronic type AF, low LAA blood flow velocity, the phenomenon of spontaneous ECHO contrast in LA and the morphological LAA type III by CT.

Full Text

Restricted Access

About the authors

Elena Z. Golukhova

Bakoulev Center for Cardiovascular Surgery RAMS

Author for correspondence.
ORCID iD: 0000-0002-6252-0322
SPIN-code: 9334-5672

Russian Federation, Moscow

MD, PhD, Professor, Academician of the RAS

Olga I. Gromova

Bakoulev Center for Cardiovascular Surgery RAMS

ORCID iD: 0000-0002-0216-1372
SPIN-code: 4715-1322

Russian Federation, Moscow

MD, PhD, Research Associate, Cardiologist

Naida I. Bulaeva

Bakoulev Center for Cardiovascular Surgery RAMS

ORCID iD: 0000-0002-5091-0518
SPIN-code: 8979-7098

Russian Federation, Moscow

MD, PhD in Biology, Senior Research Associate, Cardiologyst

Mari G. Arakelyan

Bakoulev Center for Cardiovascular Surgery RAMS

ORCID iD: 0000-0001-5089-0169
SPIN-code: 9161-9888

Russian Federation, Moscow



  1. Patel NJ, Deshmukh A, Pant S, et al. Contemporary trends of hospitalization for atrial fibrillation in the United States, 2000 through 2010 implications for healthcare planning. Circulation. 2014;129(23):2371–2379. doi:
  2. Kishore A, Vail A, Majid A, et al. Detection of atrial fibrillation after ischemic stroke or transient ischemic attack: a systematic review and meta-analysis. Stroke. 2014;45(2):520–526. doi:
  3. Grond M, Jauss M, Hamann G, et al. Improved detection of silent atrial fibrillation using 72-hour Holter ECG in patients with ischemic stroke: a prospective multicenter cohort study. Stroke. 2013;44(12):3357–3364. doi:
  4. Kirchhof P, Benussi S, Kotecha D, et al. ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS. Eur Heart J. 2016;37(38):2893–2962. doi:
  5. Fabritz L, Guasch E, Antoniades C, et al. Expert consensus document: Defining the major health modifiers causing atrial fibrillation: a roadmap to underpin personalized prevention and treatment. Nat Rev Cardiol. 2016;13(4):230–237. doi:
  6. Брель Н.K., Коков А.Н., Масенко В.Л., Груздев О.В. Оценка эпикардиального депо висцеральной жировой ткани с использованием магнитно-резонансной томографии // Лучевая диагностика и терапия. — 2017. — № 2. — С. 98–99. [Brel’ NK, Kokov AN, Masenko VL, Gruzdev OV. Ocenka epikardial’nogo depo visceral’noj zhirovoj tkani s ispol’zovaniem magnitno-rezonansnoj tomografii. Luchevaya Diagnostika i Terapiya. 2017;2;98–99. (In Russ.)] doi:
  7. Lee JJ, Yin X, Hoffmann U, et al. Relation of pericardial fat, intrathoracic fat, and abdominal visceral fat with incident atrial fibrillation (from the Framingham Heart Study). Am J Cardiol. 2016;118(10):1486–1492. doi:
  8. Latchamsetty R, Morady F. Catheter Ablation of Atrial Fibrillation. Heart Failure Clinics. 2016;12(2):223–233. doi:
  9. Goette A, Kalman JM, Aguinaga L, et al. EHRA/HRS/APHRS/SOLAECE expert consensus on Atrial cardiomyopathies: definition, characterization, and clinical implication. Europace. 2016;18(10):1455–1490. doi:
  10. Lacomis JM, Goitein O, Deible C, et al. Dynamic multidimensional imaging of the human left atrial appendage. Europace. 2007;9(12):1134–1140. doi:
  11. Wang Y, Di Biase L, Horton RP, et al. Left atrial appendage studied by computed tomography to help planning for appendage closure device placement. J Cardiovasc Electrophysiol. 2010;21(9):973–982. doi:
  12. Голухова Е.З., Громова О.И., Аракелян М.Г., и др. Предикторы тромбоза ушка левого предсердия и тромбоэмболических осложнений у больных с фибрилляцией предсердий без сопутствующей клапанной патологии и ишемической болезни сердца // Креативная кардиология. — 2017. — Т. 11. – № 3. — С. 262–272. [Goluhova EZ, Gromova OI, Arakelyan MG, et al. Risk factors of left atrial thrombus and/or thromboembolism in patients with nonvalvular, nonishemic atrial fibrillation. Kreativnaya kardiologiya. 2017;11(3):262–272. (In Russ.)] doi:
  13. Venteclef N, Guglielmi V, Balse E, et al. Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. Eur Heart J. 2015;36(13):795–805. doi:
  14. Mookadam F, Goel R, Alharthi MS, et al. Epicardial Fat and Its Association with Cardiovascular Risk: A Cross-Sectional Observational Study. Heart Views. 2010;11(3):103–108. doi:
  15. Karasoy D, Bo Jensen T, Hansen ML, et al. Obesity is a risk factor for atrial fibrillation among fertile young women: a nationwide cohort study. Europace. 2013;15(6):781–786. doi:
  16. Asghar O, Alam U, Hayat SA, et al. Obesity, diabetes and atrial fibrillation; epidemiology, mechanisms and interventions. Curr Cardiol Rev. 2012;8(4):253–264. doi:
  17. Teresa SMT, Marion EB, Yoko M, et al. Obesity as a risk factor for the progression of paroxysmal to permanent atrial fibrillation: a longitudinal cohort study of 21 years. Eur Heart J. 2008;29(18):2227–2233. doi:
  18. Ganesan AN, Chew DP, Hartshorne T, et al. The impact of atrial fibrillation type on the risk of thromboembolism, mortality, and bleeding:a systematic review and meta-analysis. Eur Heart J. 2016;37(20):1591–1602. doi:
  19. Bejinariu AG, Härtel DU, Brockmeier J, et al. Left atrial thrombi and spontaneous echo contrast in patients with atrial fibrillation: Systematic analysis of a single-center experience. Herz. 2016;41(8):706–714. doi:
  20. Handke M, Harloff A, Hetzel A, et al. Left atrial appendage flow velocity as a quantitative surrogate parameter for thromboembolic risk: determinants, and relationship to spontaneous echocontrast and thrombus formation — a transesophageal echocardiographic study in 500 patients with cerebral ischemia. J Am Soc Echocardiogr. 2005;18(12):1366–1372. doi:
  21. Zhao Y, Ji L, Liu J, et al. Intensity of Left Atrial Spontaneous Echo Contrast as a Correlate for Stroke Risk Stratification in Patients with Nonvalvular Atrial Fibrillation. Sci Rep. 2016;6:27650. doi:
  22. Di Biase L, Santangeli P, Anselmino M, et al. Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation? Results from a multicenter study. J Am Coll Cardiol. 2012;60(6):531–538. doi:
  23. Khurram IM, Dewire J, Mager M, et al. Relationship between left atrial appendage morphology and stroke in patients with atrial fibrillation. Heart Rhythm. 2013;10(12):1843–1849. doi:

Supplementary files

Supplementary Files Action
Figure: 1. Research design (own data). AF, atrial fibrillation; LAA - left atrial appendage; ONMK - acute violation of cerebral circulation; EJ - epicardial fat; LP - left atrium.

Download (381KB) Indexing metadata
Figure: 2. Morphological types of the left atrial appendage according to computed tomography [12]

Download (135KB) Indexing metadata
Figure: 3. Shapes of the left atrial appendage according to the classification of Wang et al. [11]

Download (298KB) Indexing metadata



Abstract - 1366

PDF (Russian) - 1


Article Metrics

Metrics Loading ...



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies