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Background: HFrEF patients experience long-term deterioration of autonomic function and cardiac electrical stability linked to increased sudden cardiac death risk. ANTHEM-HF (NCT01823887) reported improved baroreceptor sensitivity (heart rate turbulence, HRT), heart rate variability (rMSSD), and reduced cardiac electrical instability (T-wave alternans, TWA) after 12 months of chronic vagus nerve stimulation (VNS). It is unknown whether these benefits persist long-term.

Methods: HRT, rMSSD, TWA, and VT occurrence were evaluated during chronic VNS in all patients with symptomatic HFrEF with available 36-month follow-up data (n=25). ECGs were analyzed before Autonomic Regulation Therapy system implantation (LivaNova USA) and after chronic cervical VNS.

Results: Improvement in HRT slope persisted at 24 months (8.1±1.2 ms/RR interval, p=0.02) and 36 months (7.9±0.9 ms/RR interval, p=0.03) of VNS compared to baseline. RMSSD increase continued at 24 months (34.6±2.7 ms2, p<0.02) and 36 months (36.4±2.0 ms2, p=0.002). Peak TWA levels remained reduced at 24 months (47.8±1.3 μV, p<0.0001) and 36 months (46.1±1.6 μV, p<0.0001). No sudden death, VF, or sustained VT occurred, and patients with nonsustained VT decreased from 11 (44%) at baseline to 1 (5%) at 24 months (p<0.003) and 2 (11%) at 36 months (p<0.02).

Conclusion: In patients with HFrEF, chronic VNS appears to confer persistent 3-year improvements in autonomic tone, baroreceptor sensitivity, and cardiac electrical stability.

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