Vagus Nerve Stimulation Provides Multiyear Improvements in Autonomic Function and Cardiac Electrical Stability in the ANTHEM-HF Study

Abstract

Background: Patients with heart failure with reduced left ventricular ejection fraction (LVEF) (HFrEF) experience long-term deterioration of autonomic function and cardiac electrical stability linked to increased mortality risk. The Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Heart Failure (ANTHEM-HF) trial reported improved heart rate variability (HRV) and heart rate turbulence (HRT) and reduced T-wave alternans (TWA) after 12 months of vagus nerve stimulation (VNS). We investigated whether the benefits of chronic VNS persist in the long term. Methods and Results: Effects of chronic VNS on heart rate, HRV, HRT, TWA, R-wave and T-wave heterogeneity (RWH, TWH), and nonsustained ventricular tachycardia (NSVT) incidence were evaluated in all ANTHEM-HF patients with ambulatory ECG data at 24 and 36 months (n = 25). Autonomic markers improved significantly at 24 and 36 months compared to baseline [heart rate, square root of the mean squared differences of successive normal-to-normal intervals (rMSSD), standard deviation of the normalto-normal intervals (SDNN), HF-HRV, HRT slope, P < 0.05]. Peak TWA levels remained reduced at 24 and 36 months (P < 0.0001). Reductions in RWH and TWH at 6 and 12 months persisted at 24 and 36 months (P < 0.01). NSVT decreased at 12, 24, and 36 months (P < 0.025). No sudden cardiac deaths, ventricular fibrillation, or sustained ventricular tachycardia occurred. Conclusion:In symptomatic patients with HFrEF, chronic VNS appears to confer wide-ranging, persistent improvements in autonomic tone (HRV), baroreceptor sensitivity (HRT), and cardiac electrical stability (TWA, RWH, TWH).

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“…In the present study, LLVNS significantly prevented the incidence of VAs, which was consistent with published findings of VNS during myocardial ischemia in animal models (6)(7)(8)(9)21). Lately, Nearing et al found VNS provided cardiac electrical stability and significantly prevented non-sustained VT in the ANTHEM-HF study (14). In contrast to previous studies, the dose of LLVNS without HR changes in this study could reach the therapeutic target zone reported by previous studies and contributed to satisfactory autonomic engagement for cardiac control (18,22).…”

“…However, two large clinical trials failed to demonstrate that VNS could improve cardiac function or reduce mortality (10,11). Another study showed VNS was a promising therapy in heart failure (HF) (12)(13)(14)(15)(16). The interfaces and stimulation protocols used among the abovementioned studies were various, probably contributing to different results (17)(18)(19).…”

Vagus Nerve Stimulation in Early Stage of Acute Myocardial Infarction Prevent Ventricular Arrhythmias and Cardiac Remodeling

“…VNS has been applied as a therapy for patients with heart failure (24). However, large clinical studies on VNS have had mixed results (10)(11)(12)(13)(14)(15)(16). A posthoc analysis showed that various neural targets, VNS doses and HR responses may explain the reasons for different results (17).…”

Epileptic heart: A clinical syndromic approach

“…Pharmacological and device‐based interventions that enhance parasympathetic tone should be considered. Vagus nerve stimulation, while reducing seizure frequency, 92 protects the heart through multiple antiadrenergic, 93 antiapoptotic, 94 and anti‐inflammatory actions, 94 and through reduction in cardiac electrical instability 7,52,53,95 …”