Modulation of sympathetic nervous system activity through various therapeutic approaches in patients with resistant hypertension and heart failure with preserved ejection fraction

Abstract

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Agency for Research and Development Purpose The increased activity of the sympathetic nervous system is the pathophysiological key of several pathologies, such as hypertension, heart failure, diabetes, etc., the modulation of its activity can improve the management of these diseases and represents an increased scientific interest. Aim Comparatively evaluation of the effects of modulating SNS activity at different levels through various therapeutic approaches on the NYHA functional class of heart failure and physical capacity to exercise in patients with resistant hypertension. Material and method 75 patients with resistant hypertension and heart failure with the preserved ejection fraction were enrolled in the study. All patients for 21 days underwent standardized ambulatory treatment with Losartan 100 mg, Amlodipine 10 mg and Indapamide 1.5 mg, and were subsequently randomized into three equal groups of 25 patients according to treatment supplemented to the previous treatment: group I M - Moxonidine, group II B - Bisoprolol and group III D – renal denervation. Patients were evaluated clinically, echocardiographically and by the 6-minute walking test at baseline, 3 and 6 months. Results The clinical improvement of NYHA class was confirmed by the progressive increase of the distance traveled in the 6 minute walk test. Thus, the groups being comparable according to the distance traveled at the enrollment stage in the study, noted a statistically authentic dynamic starting with 3 months of continuous medication constituting 392.48 ± 14.88 m in the I M group (+ 20.45% from initial values ) versus 359.84 ± 15.15 m in group II B (+ 15.0% of initial values) and 386.08 ± 11.99 m in group III D (+ 24.33% of initial values), p> 0.05. The increase of the distance traveled continued until 6 months of evaluation in all three observation lots with the following values: 416.12 ± 13.50 m (+ 25.06% from the initial) versus 387.80 ± 12.85 m (+ 21.55% from the initial) and 424.28 ± 10.30 m (+ 31.06% from the initial) in lots I M, II B and III D, respectively. Comparative analysis of the dynamics between groups showed a comparable beneficial effect in improving the distance traveled in the 6 minute walk test in groups of patients treated with Moxonidine and Bisoprolol and the superiority of minimally invasive renal denervation treatment over drug treatment, an event notable starting with 3 months of evaluation and maintained until the end of the supervision period. Conclusions Blockade of the sympathetic nervous system at the central level with the selective imidazoline receptor agonist I1 Moxonidine, at the peripheral level by administration of the β1-cardioselective adrenoblocker Bisoprolol or by the minimally invasive method of renal artery denervation resulted in progresive amelioration of NYHA class and increasing physical capacity to exercise, the pharmacological treatment groups showing a comparable effect, but lower than the group of patients undergoing renal denervation.