Augmented single‐unit muscle sympathetic nerve activity in heart failure with chronic atrial fibrillation

Abstract

Non-technical summary Augmentation of sympathetic nerve activity plays an important role in the deterioration of heart failure (HF). Atrial fibrillation (AF) is a well known and common complication in chronic HF. However, it remains unclear the relationship between sympathetic nerve activity and irregular ventricular rhythm induced by AF in HF. We examined the different sympathetic firing characteristics between HF patients with and without AF using a single-unit muscle sympathetic nerve activity (MSNA) method, which is a newly developed assessment of direct recording of sympathetic nerve activity. The firing frequency of single-unit MSNA was increased in HF patients with AF compared with HF patients without AF; particularly, those with a prolonged long RR interval showed multiple firings of single-unit MSNA. More intense single-unit MSNA within one cardiac interval occurred in HF patients with AF than patients without AF, even in AF patients receiving heart rate control therapy. Accordingly, our results suggest that AF per se augments central sympathetic activity and the restoration of sinus rhythm may be more effective in the treatment of HF patients with AF.Abstract Atrial fibrillation (AF) is a common complication in heart failure (HF) patients. However, it remains unclear whether irregular ventricular response patterns induced by AF increase sympathetic nerve activity. We measured resting multi-and single-unit muscle sympathetic nerve activity (MSNA) in 21 age-matched HF patients with chronic AF (n = 11) rhythm or sinus rhythm (SR, n = 10). The multi-unit MSNA, which was expressed as total activity, was similar between HF + AF patients and HF + SR patients. However, the single-unit MSNA in HF + AF patients was significantly greater than that in HF + SR patients (62 ± 9 spikes min −1 vs. 42 ± 4 spikes min −1 , P < 0.05). Moreover, the incidence of multiple firing of single-unit MSNA within a given burst was augmented in HF + AF patients as compared with HF + SR patients (48 ± 8% vs. 26 ± 3%, P < 0.01). A significant negative relationship was observed between the reduced diastolic pressure induced by a prolonged cardiac interval in AF subjects and single-unit MSNA frequency within one cardiac interval in each HF + AF subject. The firing characteristics of single-unit MSNA were different between HF patients with AF and HF patients with SR; particularly, those with a prolonged long RR interval showed multiple firings of single-unit MSNA. These findings suggest that AF per se leads to the instantaneous augmentation of single-unit MSNA induced by decreased diastolic pressure, which might partially contribute to disease progression in HF patients.

2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation

“…Hemodynamic consequences of AF can result from a variable combination of suboptimal ventricular rate control (either too rapid or too slow), loss of coordinated atrial contraction, beat-to-beat variability in ventricular filling, and sympathetic activation (45-47). Consequences for individual patients vary, ranging from no symptoms to fatigue, palpitations, dyspnea, hypotension, syncope, or HF (48).…”

“…In patients undergoing AV nodal ablation, irregular right ventricular (RV) pacing at the same rate as regular ventricular pacing resulted in a 15% reduction in cardiac output (60). Irregular R-R intervals also promote sympathetic activation (45, 46). …”

Single-Unit Muscle Sympathetic Nerve Activity Reflects Sleep Apnea Severity, Especially in Severe Obstructive Sleep Apnea Patients

“…Multi-unit MSNA frequency (BF) and incidence (BI) are generally used to assess sympathetic nerve activity quantitatively; however, the multi-unit MSNA index may underestimate the actual degree of central sympathetic nerve signaling to peripheral organs. Recently, we demonstrated that single-unit MSNA is more accurate than multi-unit MSNA, especially in intense sympathoexcitation states such as heart failure (Murai et al, 2006 , 2009 ; Ikeda et al, 2012 ). Elam et al ( 2002 ) reported that the number of multiple firings during one cardiac interval in OSAS patients was significantly increased compared with systolic heart failure (HF) patients, although multi-unit MSNA levels were similar between groups.…”

Restoring Sinus Rhythm Improves Baroreflex Function in Patients With Persistent Atrial Fibrillation

“…While there are several studies evaluating the role of the autonomic nervous system in the genesis of AF, there are only limited studies evaluating the effects of AF on sympathetic activity and baroreflex function. 3,[11][12][13][14] In the acute setting, we had previously shown that induced AF was associated with a 71% increase in sympathetic nerve activity (SNA) and that the variability in RR intervals played a major role in mediating the reflex sympathoexcitation. 4 Interestingly, the increase in SNA was seen despite an increase in central venous pressure and absence of a significant decrease in BP, suggesting minimal contribution of the cardiopulmonary baroreflex and a presumed arterial baroreflex-mediated mechanism independent of mean BP.…”