Sympathetic nervous system drive assessed by direct muscle sympathetic nerve activity in heart failure: first direct human evidence of sympathetic neural surge during acute heart failure

Background Heart failure (HF) affects over 64 million people worldwide and remains associated with high morbidity, mortality, and healthcare costs. Acute heart failure (AHF) represents a sudden or progressive deterioration of HF requiring urgent medical care. [1] Although chronic sympathetic nervous system (SNS) overactivation is a well-established hallmark of HF pathophysiology, direct human evidence of sympathetic neural activity during acute HF 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 within-subject comparison. MSNA was recorded from the peroneal nerve under standardized conditions. Burst frequency (BF), burst incidence (BI; bursts/100 heartbeats), and total activity (TA = BF × mean burst height) were quantified. Paired comparisons were performed using Student’s t-tests. For contextual comparison, baseline AHF values were compared with previously published summary statistics from patients with stable chronic HF reported by Badrov et al. [2] Results Among the eight patients with paired recordings, a consistent reduction in sympathetic neural outflow was observed following clinical stabilization. BF decreased from 69.0 ± 18.7 during acute HF to 56.7 ± 17.8 bursts/min at follow-up (p = 0.04). TA decreased from 3618 ± 1201 to 2907 ± 1047 arbitrary units (p = 0.04). BI declined from 80.9 ± 14.8 to 73.5 ± 24.3 bursts/100 heartbeats, but this change did not reach statistical significance (p = 0.30). Six of eight patients (75%) demonstrated a reduction in BI. Compared with published data from stable chronic HF [2], BF during AHF was higher (63.3 ± 15.5 vs. 52 ± 15 bursts/min; p = 0.005), whereas BI did not differ significantly (76.0 ± 16.9 vs. 72 ± 19 bursts/100 heartbeats; p = 0.34). Conclusions Acute HF decompensation is characterized by a marked surge in sympathetic neural outflow that significantly subsides after clinical stabilization. Direct microneurographic recordings demonstrate reductions in both burst frequency and total sympathetic activity during recovery. These findings provide direct human evidence linking acute HF episodes with excessive sympathetic activation and identify dynamic SNS modulation as a potential mechanistic contributor to HF destabilization.Figure 1Table 1