Favorable effects of sacubitril/valsartan treatment on cardiac autonomic function parameters in patients with heart failure and reduced ejection fraction

Abstract

Heart failure with reduced ejection fraction (HFrEF) is associated with potentialy deleterious imbalance of the cardiac autonomic nervous system (CANS). In patients with HFrEF, defined as EF bellow 40%, the total sympathetic nervous activity is augmented owing to loose of baroreflex sensitivity and to increased sympathetic afferent activity. Sacubitril/valsartan (S/V) therapy leads to a favorable modulation of CANS by increasing parasympathetic activity and represent a treatment for HFrEF which impressively impacts cardiovascular outcome .

The present study aims to assess effects of S/V therapy on heart rate variabiltiy (HRV) parameters in patients with HFrEF, such as SDNN (standard deviation of normal-to-normal intervals), RMSSD (mean square of differences between consecutive R-R intervals), and frequency –domain parameters ( HF- high Frequency and LF - low Frequency) as noninvasives measures of the CANS before and after initiation of S/V therapy.

35 patients, middle age 68,9±7,8 year, underwent standardized 12-lead Holter-ECG, echocardiography and laboratory testing before and 3 months after start of therapy. S/V therapy increased SDNN (69,6±19,2 ms vs. 97,3±26,92ms p<0,01), RMSSD (16,9±4,7ms vs. 28,7±9,7 ms p<0,01) , LF power (164,2 ms²±76,2 ms² vs. 276,2±104,8 m² p<0,01) and HF power (98,5±32,8 ms² vs. 215,1±83,6 ms² p<0,01)

Echocardiography demonstrated a sinignificant increase in left ventricular ejection fraction (31,2±8,8% vs. 42,6±11,1% p<0,01) along with a significant reduction in left ventricular end dyastolic (89,08±17,7 ml/m² vs. 67,5±16,4 ml/m² p<0,01) and endsystolic volume index (59,4±18,2 ml/m² vs. 45,6±18,6 ml/m² p<0,01)

These findings were accompanied by reduced plasma NT-pro-BNP levels (2761,6 ±2503,4 ng/L vs. 830,22±567,2 ng/L p<0,01)

Three monts of S/V therapy resulted in a significant increase in cardiac parasympathetic tone. In our study we concluded also that LVEF improved and plasma level of NT-pro-BNP fell in accordance with HRV change