THE EFFECT OF ALDOSTERONE ANTAGONISTS ON THE ELECTROPHYSIOLOGICAL PARAMETERS IN RECURRENCE ATRIAL FIBRILLATION

Purpose: to investigate the effect of mineralocorticoid receptor antagonists on atrial electrophysiological parameters and frequency of AF episodes in recurrence AF and left ventricular diastolic dysfunction.

Material and methods: prospective cohort study included 89 patients with recurrence non-valvular AF and left ventricular diastolic dysfunction who had sinus rhythm at baseline. All patients received ACE inhibitors, β-blockers, statins, antithrombotic and  antiarrhythmic  drugs  and  were randomly  assigned to  either  standard  therapy  only (Control  group,  46 patients)  or mineralocorticoid receptor antagonists spironolactone 25 mg titrated to 50 mg (SPRL group, 43 patients) added to standard treatment.  At baseline and after 6 months of treatment P-wave duration and dispersion of standard electrocardiogram (ECG), P-wave signal-averaged ECG parameters (total filtered P-wave duration (FiP) and a root-mean-squared voltage of the terminal 20 ms (RMS-20) and atrial late potentials (ALP) were evaluated. The primary endpoint of the study was AF recurrence.

Results: at baseline there were no significant differences between groups. After 6 months of treatment significant reduction in P-wave dispersion were found in SPRL group. FiP improved significantly in both groups, but more in the SPRL group, RMS-20 increased only in the SPRL group. At baseline ALP was detected in 38 (82.6%) patients in Control group and in 36 (83.7%) of SPRL group (χ2 = 0.02, p = 0.887). After 6 months the ALP rate was significantly decreased in SPRL group (56.1%, χ2 = 6.4, p = 0.011 compared to baseline) but remained high in Control (76.0%, χ2 = 0.27, p = 0.6). AF recurrences were documented in 33 (71.7%, 95% CI 57.6-84.0%) patients in Control group and in 21 (48.8%, 95% CI 33.7-64.0%) in SPRL group (χ2 = 3.97, p = 0.046). Additional spironolactone intake was associated with 22.9% (95% CI 2.6-40.8%, p = 0,048) risk reduction of AF recurrence.

Summary: application of spironolactone for 6 months additionally to standard therapy in patients with recurrent AF and left ventricular diastolic dysfunction leads to significant improvement in the atrial electrophysiological parameters and decrease in AF recurrence.

1. Национальные рекомендации по диагностике и лечению фибрилляции предсердий (2012) // Российский кардиологический журнал. – 2013. – № 4 (102). – Приложение 3.

2. From changes in local RAAS to structural remodeling of the left atrium: A beautiful cycle in atrial fibrillation / Q. Yongjun, S. Huanzhang, Z. Wenxia et al. // Herz. – 2015. – Vol. 40(3). – P. 514-520.

3. Aldosterone promotes atrial fibrillation / J.C. Reil, M. Hohl, S. Selejan et al. // Eur. Heart J. – 2012. – Vol. 33(16). – P. 2098-2108.

4. Effects of spironolactone on electrical and structural remodeling of atrium in congestive heart failure dogs / S.S. Yang, W. Han, H.Y. Zhou et al. // Chin. Med. J. – 2008. – Vol. 121(1). – P. 38-42.

5. Effects of haemodialysis on maximum P wave duration and P wave dispersion / Z. Szabó, G. Kakuk, T. Fülöp et al. // Nephrol. Dial. Transplant. – 2002. – Vol. 17. – P. 1634-1638.

6. Электрофизиологическое ремоделирование миокарда: определение и применение понятия в клинической практике / Г.Г. Иванов, А.С. Аксельрод, Б.А. Трегубов и др. // Функциональная диагностика. – 2003. - № 1. – С. 320–325.

7. Mayyas, F. Impact of aldosterone antagonists on the substrate for atrial fibrillation: aldosterone promotes oxidative stress and atrial structural/electrical remodeling / F. Mayyas, K.H. Alzoubi, D.R. Van Wagoner // Int. J. Cardiol. – 2013. – Vol. 168(6). – P. 5135-5142.

8. The mineralocorticoid receptor promotes fibrotic remodeling in atrial fibrillation / D. Lavall, C. Selzer, P. Schuster et al. // J. Biol. Chem. – 2014. – Vol. 289(10). – P. 6656-6668.

9. Головач, И.Ю. Ядерный фактор κB (NF-κB) как важный патогенетический фактор и новая мишень в лечении ревматических заболеваний / И.Ю. Головач // Рациональная фармакотерапия. – 2012. – № 3. – С. 46-51.

10. Aldosterone increases T-type calcium channel expression and in vitro beating frequency in neonatal ratcardiomyocytes / N. Lalevée, M.C. Rebsamen, S. Barrère-Lemaire et al. // Cardiovasc. Res. –2005. – Vol. 67(2). – C. 216-224.