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Left Atrial Function in Different Modes of Heart-Rate Lowering Therapy with Beta-Blockers in Patients with Recurrent Atrial Fibrillation and Hypertension

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Aim. To study the impact of heart rate (HR) reduction with beta-blockers (BB) on left atrial (LA) function in hypertensive patients with paroxysmal or persistent mild symptomatic atrial fibrillation.

Material and methods. In this open prospective trial we randomly assigned patients with hypertension, sinus rhythm, elevated heart rate (≥70 bpm), and recurrent atrial fibrillation (EHRA 2A or less) to receive BB with a target HR of less or greater than 70 bpm for at least 4 months. All the patients underwent an echocardiogram [left atrial (LA) function was assessed as emptying fraction]and applanation tonometry at baseline and after 4 months. Primary endpoint was median LA emptying fraction (LAEF) measurement at the end of the study.

Results. 47 patients were randomized to group with a target HR of ≤70 bpm and 44 patients to >70 bmp. Among them 44 and 41 patients completed the study. Median follow up was 4.4 months. At the end of the study (4.5 months) median HR was 62 [60; 67] bmp in ≤70 group and 73 [72; 76] bpm in >70 group. Both groups received similar antihypertensive therapy and there were no intergroup differences in systolic and diastolic blood pressure. At the end of the study, patients in ≤70 group had significantly lower LAEF compared with >70 group (37% vs 42%; p=0.01). E’avg was lower and augmentation index was higher in ≤70 group as compared to >70. In regression analysis, after E’avg and augmentation index were included in the model, the association between LAEF and randomization group lost its significance.

Conclusion. Beta blockers treatment with strict HR reduction (≤70 bpm) significantly reduced LA function as compared to lenient target HR (>70 bpm).

About the Authors

E. V. Kokhan
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Elizaveta V. Kokhan - eLibrary SPIN 1307-6750


G. K. Kiyakbaev
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Gayrat K. Kiyakbaev - eLibrary SPIN 3192-2303


E. M. Ozova
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Elena M. Ozova - eLibrary SPIN 1160-8633


V. A. Romanova
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Vera A. Romanova


Zh. D. Kobalava
Peoples Friendship University of Russia (RUDN University)
Russian Federation

Zhanna D. Kobalava - eLibrary SPIN 9828-5409



1. Kannel WB, Kannel C, Paffenbarger R, Cupples L. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J. 1987;113(6):1489-94. DOI:10.1016/0002-8703(87)90666-1.

2. Yu J, Dai L, Zhao Q, et al. Association of Cumulative Exposure to Resting Heart Rate with Risk of Stroke in General Population: The Kailuan Cohort Study. J Stroke Cerebrovasc Dis. 2017;26(11):2501-9. DOI:10.1016/j.jstrokecerebrovasdis.2017.05.037.

3. Gillman M, Kannel W, Belanger A, D’Agostino R. Influence of heart rate on mortality among persons with hypertension: the Framingham Study. Am Heart J. 1993;125(4):1148-54. DOI:10.1016/0002-8703(93)90128-V.

4. Kjekshus J, Gullestad L. Heart rate as a therapeutic target in heart failure. Eur Heart J. 1999;1(suppl. H):H64-69.

5. Cleland J, Bunting K, Flather M, et al. Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials. Eur Heart J. 2018;39(1):26-35. DOI:10.1093/eurheartj/ehx564.

6. Kokhan EV, Kiyakbaev GK, Kobalava ZhD. Elevated heart rate in hypertension and coronary artery disease: risk factor or risk marker in patients with preserved left ventricular ejection fraction. Arterial’naya Gipertenziya. 2019;25(4):389-406 (In Russ.) DOI:10.18705/1607-419X-2019-25-4-389-406.

7. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021-104. DOI:10.1093/eurheartj/ehy339.

8. Dahlöf B, Devereux R, Kjeldsen S, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomized trial against atenolol. Lancet. 2002;359(9311):995-1003. DOI:10.1016/S0140-6736(02)08089-3.

9. Dahlöf B, Sever P, Poulter N, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicenter randomised controlled trial. Lancet. 2005;366(9489):895-906. DOI:10.1016/S0140-6736(05)67185-1.

10. Bangalore S, Sawhney S, Messerli F. Relation of Beta-Blocker-Induced Heart Rate Lowering and Cardioprotection in Hypertension. J Am Coll Cardiol. 2008;52(18):1482-9. DOI:10.1016/j.jacc.2008.06.048.

11. Williams B, Lacy P, CAFE and the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) Investigators. Impact of Heart Rate on Central Aortic Pressures and Hemodynamics. J Am Coll Cardiol. 2009;54(8):705-13. DOI:10.1016/j.jacc.2009.02.088.

12. Messerli F, Rimoldi S, Bangalore S, et al. When an Increase in Central Systolic Pressure Overrides the Benefits of Heart Rate Lowering. J Am Coll Cardiol. 2016;68(7):754-62. DOI:10.1016/j.jacc.2016.03.610.

13. Sardana M, Syed A, Hashmath Z, et al. Beta‐Blocker Use Is Associated With Impaired Left Atrial Function in Hypertension. J Am Heart Assoc. 2017;6(2):e0055163. DOI:10.1161/JAHA.116.005163.

14. Kotecha D, Melanie C, Deeks JJ, et al. A review of rate control in atrial fibrillation, and the rationale and protocol for the RATE-AF trial. BMJ Open. 2017;7(7):e015099. DOI:10.1136/bmjopen-2016-015099.

15. Paul L, Hastie C, Li W, et al. Resting heart rate pattern during follow-up and mortality in hypertensive patients. Hypertension. 2010;55(2):567-74. DOI:10.1161/HYPERTENSIONAHA.109.144808.

16. Lonn E, Rambihar S, Gao P, et al. Heart rate is associated with increased risk of major cardiovascular events, cardiovascular and all-cause death in patients with stable chronic cardiovascular disease: an analysis of ONTARGET/TRANSCEND. Clin Res Cardiol. 2014;103(2):149-59. DOI:10.1007/s00392-013-0644-4.

17. Olsen FJ, Møgelvang R, Jensen GB, et al. Relationship Between Left Atrial Functional Measures and Incident Atrial Fibrillation in the General Population: The Copenhagen City Heart Study. JACC Cardiovasc Imaging. 2019;12(6):981-9. DOI:10.1016/j.jcmg.2017.12.016.

18. Chou CC, Lee HL, Chang PC, et al. Left atrial emptying fraction predicts recurrence of atrial fibrillation after radiofrequency catheter ablation. PLoS One. 2018;13(1). DOI:10.1371/journal.pone.0191196.

19. Kanagala P, Arnold JR, Cheng ASH, et al. Left atrial ejection fraction and outcomes in heart failure with preserved ejection fraction. Int J Cardiovasc Imaging. 2020;36(1):101-10. DOI:10.1007/s10554-019-01684-9.

20. Andersen D, Jensen JS, Mogelvang R, et al. The left atrium emptying fraction as a predictor of cardiovascular morbidity and mortality in a low risk general population. J Am Coll Cardiol. 2017;69(11):1536. DOI:10.1016/s0735-1097(17)34925-2.

21. Gupta S, Matulevicius SA, Ayers CR, et al. Left atrial structure and function and clinical outcomes in the general population. Eur Heart J. 2013;34(4):278-85. DOI:10.1093/eurheartj/ehs188.

22. Komajda M, Isnard R, Cohen-Solal A, et al. Effect of ivabradine in patients with heart failure with preserved ejection fraction: the EDIFY randomized placebo-controlled trial. Eur J Heart Fail. 2017;19(11):1495-503. DOI:10.1002/ejhf.876.

23. Boutouyrie P, Achouba A, Trunet P, et al. Amlodipine-Valsartan Combination Decreases Central Systolic Blood Pressure More Effectively Than the Amlodipine-Atenolol Combination. Hypertension. 2010;55(6):1314-22. DOI:10.1161/HYPERTENSIONAHA.109.148999.

24. London G, Asmar R, O’Rourke M, et al. Mechanism(s) of selective systolic blood pressure reduction after a low-dose combination of perindopril/indapamide in hypertensive subjects: comparison with atenolol. J Am Coll Cardiol. 2004;43(1):92-9. DOI:10.1016/j.jacc.2003.07.039.

25. Goupil R, Dupuis D, Troyanov S, et al. Heart rate dependent and independent effects of beta-blockers on central hemodynamic parameters. J Hypertens. 2016;34(8):1535-43. DOI:10.1097/HJH.0000000000000978.

For citation:

Kokhan E.V., Kiyakbaev G.K., Ozova E.M., Romanova V.A., Kobalava Zh.D. Left Atrial Function in Different Modes of Heart-Rate Lowering Therapy with Beta-Blockers in Patients with Recurrent Atrial Fibrillation and Hypertension. Rational Pharmacotherapy in Cardiology. 2021;17(3):429-437. (In Russ.)

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)