Autonomic regulation therapy in chronic heart failure with preserved/mildly reduced ejection fraction: ANTHEM-HFpEF study results

• Published in: International journal of cardiology Vol. 381; pp. 37 - 44
• Main Authors: Kumar, H. Uday, Nearing, Bruce D., Mittal, Sanjay, Premchand, Rajendra K., Libbus, Imad, DiCarlo, Lorenzo A., Amurthur, Badri, KenKnight, Bruce H., Anand, Inder S., Verrier, Richard L.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.06.2023
• Subjects: Arrhythmias, Cardiac; Autonomic regulation therapy; Chronic Disease; Female; Heart; Heart Diseases; Heart failure; Heart Failure - drug therapy; Heart Failure - therapy; Humans; Mildly reduced ejection fraction; Preserved ejection fraction; Prognosis; Quality of Life; Stroke Volume - physiology; T-wave alternans; Treatment Outcome; Vagus nerve stimulation; Ventricular Dysfunction, Left; Ventricular Function, Left - physiology; Heart failure; Vagus nerve stimulation; Preserved ejection fraction; T-wave alternans; Mildly reduced ejection fraction; Autonomic regulation therapy
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2023.03.030

Autonomic regulation therapy (ART) utilizing cervical vagus nerve stimulation (VNS) appeared to be safe and to improve autonomic tone, symptoms, and cardiac mechanical function in patients with symptomatic heart failure and reduced ejection fraction in the ANTHEM-HF Study. The ANTHEM-HFpEF Study is the first investigation to evaluate the safety and feasibility of ART in patients with symptomatic heart failure and preserved or mildly reduced ejection fraction (HFpEF, HFmrEF). This open-label interventional study enrolled 52 patients with HFpEF or HFmrEF, NYHA Class II-III, and LVEF ≥40%, who received stable guideline-directed medical therapy. All patients were successfully implanted with LivaNova VNS Therapy® system with an electrical lead surrounding the right cervical vagus nerve. Adverse event incidence was low. At 12 months, NYHA class (p <0.0001), 6-min walk distance (p <0.05), and quality of life (p <0.0001) were improved. Cardiac mechanical function measures were normal at baseline, except for left ventricular mass index in women and E/e' ratio in all patients, which were elevated at baseline, and were unchanged by ART. Autonomic tone and reflexes improved, indicated by 29% decrease in low-frequency/high-frequency heart rate variability to normal levels (p = 0.028) and by increased heart rate turbulence slope (p = 0.047). T-wave alternans (p = 0.001) and T-wave heterogeneity (p = 0.001) were reduced from abnormal to normal ranges. Nonsustained ventricular tachycardia incidence decreased (p = 0.027). ART appeared well-tolerated and safe in patients with HFpEF or HFmrEF. Chronic ART did not alter mechanical function measures but was associated with improved heart failure symptoms, exercise tolerance, autonomic tone, and cardiac electrical stability. Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Heart Failure with Preserved Ejection Fraction [ClinicalTrials.gov #NCT03163030, registered 05/22/2017]. [Display omitted] •This is the first study to evaluate the safety and feasibility of chronic autonomic regulation therapy (ART) using cervical vagus nerve stimulation (VNS) in patients with heart failure with preserved or mildly reduced ejection fraction (HFpEF or HFmrEF).•ART utilizing VNS appears to be well-tolerated and safe in patients with HFpEF or HFmrEF as it did not alter cardiac mechanical function measures.•Moreover, chronic ART with VNS improved NYHA class (p < 0.0001), 6-min walk distance (p < 0.05), quality of life (p < 0.0001), and autonomic tone (p=0.028) and reflexes (p=0.047), and reduced T-wave alternans (p = 0.001) and T-wave heterogeneity (p = 0.001) from abnormal to normal ranges. Number of patients with nonsustained ventricular tachycardia (NSVT) incidence decreased (p = 0.027).•The benefits of chronic ART on NYHA Class, TWA, and TWH, were evident in both HFpEF and HFmrEF patients. Number of HFmrEF patients with NSVT was reduced (p-0.0434).