Aortic thoracic neuromodulation in heart failure with preserved ejection fraction

Abstract

The inadequacy of medical therapies for heart failure with preserved ejection fraction (HFpEF) is driving the development of device‐based solutions targeting underlying pathophysiologic abnormalities. The maladaptive autonomic imbalance with a reduction in vagal parasympathetic activity and increased sympathetic signalling contributes to the deterioration of cardiac performance, patient fitness, and the increased overall morbidity and mortality. Thoracic aortic vagal afferents mediate parasympathetic signalling, and their stimulation has been postulated to restore autonomic balance. In this first‐in‐man experience with chronic stimulation of aortic vagal afferents (Harmony™ System, Enopace, Israel), we demonstrate improved left atrial remodelling and function parallel with improved left ventricular performance. The observed favourable structural and functional cardiac changes remained stable throughout the 1 year follow‐up and were associated with improved symptoms and physical fitness. The current experience warrants further validation of the endovascular stimulation of aortic thoracic afferents as a new interventional approach for device‐based treatment in HFpEF.

Neuromodulation interventions in the management of heart failure

“…39,40 In addition, the vagal aortic afferent nerves, located in the upper part of the thoracic aorta, mediate parasympathetic neuronal transmission to the brain. [39][40][41] Device-based aortic stimulation targets these vagal afferents (mechanoreceptors) in the descending aorta to modulate parasympathetic tone via chronic stimulation. The Endovascular NeuromoDulation Treatment for Heart Failure Patients (ENDO-HF, NCT02633644) feasibility study evaluates the safety and feasibility of the Harmony aortic stimulation system in the treatment of up to 20 patients with HF over 5 years of follow-up.…”

“…Long-term stimulation aims at decreasing sympathetic tone and increasing parasympathetic tone, resulting in lowering of heart rate and LV afterload. 41 However, according to the United States Clinical Trials Registry, the ENDO-HF trial has been terminated. 42…”

“…Ventricular–arterial coupling (which characterizes the interaction between the contractile function of the myocardium and the arterial circulatory load) and aortic compliance are controlled by aortic endothelial cells and neural parasympathetic transmission, which are involved in the maintenance of autonomic balance 39,40 . In addition, the vagal aortic afferent nerves, located in the upper part of the thoracic aorta, mediate parasympathetic neuronal transmission to the brain 39–41 . Device‐based aortic stimulation targets these vagal afferents (mechanoreceptors) in the descending aorta to modulate parasympathetic tone via chronic stimulation.…”

“…This self‐expandable stent is implanted in the descending aorta after verification of response to stimulation with an acute decrease in heart rate. Long‐term stimulation aims at decreasing sympathetic tone and increasing parasympathetic tone, resulting in lowering of heart rate and LV afterload 41 . However, according to the United States Clinical Trials Registry, the ENDO‐HF trial has been terminated 42…”

Pharmacological and Non-Pharmacological Advancements in Heart Failure Treatment

“…It comprises an implantable unit, delivery catheter, patient wearable unit, and programming unit. In this study, chronic stimulation of aortic vagal afferents using this system has been shown to improve left atrial remodeling and function, as well as left ventricular performance, highlighting the potential of neuromodulation therapy as an effective treatment for HFpEF [ 51 ].…”