Sympathetic and baroreflex alterations in congestive heart failure with preserved, midrange and reduced ejection fraction

Aim: Although abnormalities in reflex sympathetic neural function represent a hallmark of heart failure, no information is available on the neuroadrenergic and baroreflex function in heart failure with preserved, midrange and reduced ejection fraction. The current study was designed to assess muscle sympathetic nerve traffic (MSNA) and baroreflex function in the clinical classes of heart failure defined by the new European Society of Cardiology/American College of Cardiology Foundation/American Heart Association guidelines. Methods: In 32 treated heart failure patients aged 69.3 +/- 1.1 (mean +/- SEM) classified according to new heart failure guidelines, we measured MSNA (microneurography), spontaneous baroreflex sensitivity and venous plasma norepinephrine (HPLC). Fourteen age-matched healthy individuals represented the control group. Results: MSNA was progressively and significantly increased from controls to heart failure conditions characterized by preserved, midrange and reduced ejection fraction (40.4 +/- 2.5, 55.6 +/- 2.1, 70.4 +/- 3 and 78.6 +/- 2.6 bursts/100 heart beats, P < 0.01). In contrast, plasma norepinephrine was significantly increased in heart failure with reduced ejection fraction only. Baroreflex sensitivity was significantly reduced in the latter two clinical conditions and almost unaltered in heart failure with preserved ejection fraction. There was an inverse relationship between different markers of adrenergic activity (MSNA, heart rate and plasma norepinephrine), left ventricular ejection fraction and baroreflex function. Brain natriuretic peptides were directly and significantly related to MSNA and plasma norepinephrine. Conclusion: Thus clinical categories of heart failure patients defined by the new European Society of Cardiology/American College of Cardiology Foundation/American Heart Association classification share as a common pathophysiological link the marked overactivity of the sympathetic nervous system, whose magnitude is significantly and strongly related to the impairment of the left ventricular ejection fraction. A baroreflex dysfunction accompanies in the more severe heart failure state the neuroadrenergic activation.