Sympathetic nervous system drive assessed by direct muscle sympathetic nerve activity in heart failure: first-in-human insights into autonomic regulation in acute vs. chronic states

Background

Heart failure (HF) affects over 64 million people worldwide and is associated with high morbidity, mortality, and healthcare costs. Acute heart failure (AHF) represents a sudden or progressive deterioration of HF requiring urgent medical care. Excessive activation of the sympathetic nervous system (SNS) has been believed to be a key pathophysiological feature of HF, yet direct evidence of sympathetic overactivity during acute decompensation is lacking.

Purpose

To directly assess and compare sympathetic nervous system activity using microneurographic recordings of muscle sympathetic nerve activity (MSNA) in patients during acute HF decompensation and after clinical stabilization.

Methods

In this prospective mechanistic study, 20 patients hospitalized with AHF underwent MSNA recordings within 48 hours of admission. In eight patients, repeat recordings were performed 4–20 weeks after clinical stabilization (median [IQR]: 11.4 [8.1–16.8] weeks), allowing for direct within-subject comparison. Ten patients with stable chronic HF served as a reference group. MSNA was recorded from the peroneal nerve under standardized conditions, and burst frequency, burst incidence and total activity were quantified.

Results

Among the eight patients with paired MSNA recordings at follow-up, a consistent reduction in sympathetic neural outflow was observed following clinical stabilization (Table 1, Figure 1). Muscle sympathetic nerve activity expressed as burst frequency (BF) decreased from 69.0±18.7 during acute HF to 56.7±17.8 bursts/min at follow-up, p=0.04.

Total activity (TA), calculated as the product of burst frequency and mean burst height (TA = BF × MBH), and therefore reflecting both the rate and amplitude of sympathetic bursts, decreased significantly from 3618 ± 1201 to 2907 ± 1047 arbitrary units p = 0.04.

Conclusions

Acute HF decompensation is characterized by a marked surge in sympathetic neural outflow, which significantly subsides after clinical stabilization. Direct microneurographic recordings demonstrate a consistent reduction in MSNA, including both burst frequency and total activity, during recovery. These data provide direct human evidence linking acute HF decompensation with excessive sympathetic activation and identify the SNS as a critical contributor to HF destabilization.Figure 1For image description, please refer to the figure legend and surrounding text.Table 1 For image description, please refer to the figure legend and surrounding text.