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.

Keywords: Aortic thoracic neuromodulation; Autonomic imbalance; Enopace; Harmony™ system; Heart failure with preserved ejection fraction (HFpEF).

Figure 1

(A) Nitinol stent‐like device bearing four stimulation platinum/iridium electrodes, a receiving RF antenna coil (gold covered with Ethylene/PTFE), a titanium sealed electrical circuit unit implanted in the target aortic area after checking an adequate response in mean aortic pressure drop. (B) Baseline versus 6 month and 1 year improvements in functional capacity with increase in 6 min walking test (from 357 m at baseline to 419 m) and decrease of NT proBNP (from 703 to 502 pg/mL) without any change in renal function (GFR > 60 mL/min), allowing to reduce bumetanide and spironolactone. (C, D) Baseline versus 1 year improvement of GLS, GWI, and GWE. BL, baseline; NT‐proBNP, N‐terminal prohormone of brain natriuretic peptide; GFR, glomerular filtration rate; BP, blood pressure; GLS, left ventricular global longitudinal strain; GWI, left ventricular non‐invasive global work index; GWE, left ventricular non‐invasive global work efficacy; GCW, left ventricular non‐invasive global constructive work; GWW, left ventricular non‐invasive global wasted work.