Autonomic regulation therapy to enhance myocardial function in heart failure patients: the ANTHEM‐HFpEF study

Abstract

BackgroundApproximately half of the patients presenting with new‐onset heart failure (HF) have HF with preserved left ventricular ejection fraction (HFpEF) and HF with mid‐range left ventricular ejection fraction (HFmrEF). These patients have neurohormonal activation like that of HF with reduced ejection fraction; however, beta‐blockers and angiotensin‐converting enzyme inhibitors have not been shown to improve their outcomes, and current treatment for these patients is symptom based and empiric. Sympathoinhibition using parasympathetic stimulation has been shown to improve central and peripheral aspects of the cardiac nervous system, reflex control, induce myocyte cardioprotection, and can lead to regression of left ventricular hypertrophy. Beneficial effects of autonomic regulation therapy (ART) using vagus nerve stimulation (VNS) have also been observed in several animal models of HFpEF, suggesting a potential role for ART in patients with this disease.MethodsThe Autonomic Neural Regulation Therapy to Enhance Myocardial Function in Patients with Heart Failure and Preserved Ejection Fraction (ANTHEM‐HFpEF) study is designed to evaluate the feasibility, tolerability, and safety of ART using right cervical VNS in patients with chronic, stable HFpEF and HFmrEF. Patients with symptomatic HF and HFpEF or HFmrEF fulfilling the enrolment criteria will receive chronic ART with a subcutaneous VNS system attached to the right cervical vagus nerve. Safety parameters will be continuously monitored, and cardiac function and HF symptoms will be assessed every 3 months during a post‐titration follow‐up period of at least 12 months.ConclusionsThe ANTHEM‐HFpEF study is likely to provide valuable information intended to expand our understanding of the potential role of ART in patients with chronic symptomatic HFpEF and HFmrEF.

Low‐level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction

“…In addition, IL‐1 blockade with anakinra in patients with HFpEF improved peak oxygen consumption in a recent randomized cross‐over trial (Van Tassell et al., ). In support of the notion that autonomic stimulation may be an attractive non‐pharmacological approach to treat patients with HFpEF, an ongoing clinical study (ANTHEM‐HFpEF) is designed to evaluate the feasibility, tolerability and safety of right cervical VNS in patients with symptomatic HFpEF (DiCarlo et al., ).…”

The functional consequences of sodium channel NaV1.8 in human left ventricular hypertrophy

“…3,4 Furthermore, it has been shown that structural modifications due to LVH are associated with HF with preserved ejection fraction (HFpEF). 10,11 Patients with severe aortic stenosis-dependent symptoms have a tremendous risk of sudden cardiac death if only medically treated. [6][7][8][9] The pathology of LVH shows not only mechanical but also extensive cellular and molecular remodelling including cardiomyocyte growth changes, dysfunction of excitationcontraction coupling, certain metabolic dysfunctions, and fibrosis.…”

“…[6][7][8][9] The pathology of LVH shows not only mechanical but also extensive cellular and molecular remodelling including cardiomyocyte growth changes, dysfunction of excitationcontraction coupling, certain metabolic dysfunctions, and fibrosis. 10,11 Patients with severe aortic stenosis-dependent symptoms have a tremendous risk of sudden cardiac death if only medically treated. 12 In the past few decades, a great progress has been made in underpinning the cellular and molecular mechanisms of remodelling in myocardial hypertrophy.…”

Calming the Nervous Heart: Autonomic Therapies in Heart Failure

“…However, primarily because of off-target effects, stimulus intensity was ~1.4 mA, which is in the region below the neural fulcrum and sub-threshold for optimal stimulation (Figure 3). 40 In an analysis of 87 of the 96 patients implanted with available data, there was no statistically significant change in the primary endpoint of LVESD. Regarding adverse events, one patient died in the postoperative period from a pulmonary embolism, and there were three patient deaths between randomisation and 6 months as a result of worsening HF or HF complications.…”

“…The NEural Cardiac TherApy foR HF (NECTAR-HF) study was a randomised, shamcontrolled trial that evaluated the utility of VNS using the Precision Spectra™ system (Boston Scientific; St Paul, MN, USA). 40 In this study, 96 patients with NYHA functional class II-III symptoms, LVEF ≤35 % and LVEDD ≥55 mm were randomised to VNS or control (device implanted but VNS off) in a 2:1 ratio for a 6-month period. Stimulation intensity was titrated, as tolerated, with a target of 20 Hz, a duty cycle of 16.7 %, a pulse width of 300 µs and a proposed maximal current intensity of 4 mA.…”