The role of neuromodulation in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome with limited treatment options to improve long-term outcomes such as quality of life, exercise capacity, and mortality. Neuromodulation-based therapies have emerged as potential interventions to address autonomic dysregulation in HFpEF. This review discusses the long-term efficacy and safety of four key neuromodulation therapies: Renal Denervation (RDN), Baroreceptor Activation Therapy (BAT), Vagus Nerve Stimulation (VNS), and Greater Splanchnic Nerve (GSN) Ablation. Each therapy shows promise, but variability exists in terms of patient outcomes, procedural risks, and long-term durability. This paper evaluates the pros and cons of each approach, focusing on their potential to improve clinical outcomes in diverse HFpEF phenotypes.

To summarise and critically assess the role of neuromodulation-based devices in managing HFpEF, including their mechanisms, efficacy, and impact on patient outcomes.

We reviewed clinical trials and studies involving neuromodulation therapies for HFpEF, focusing on VNS, RDN, BAT, and GSN. The review includes randomised controlled trials and feasibility studies assessing various endpoints such as functional status, QoL, exercise capacity, and adverse events.

Neuromodulation therapies show potential in improving symptoms and QoL for HFpEF patients. The ANTHEM-HFpEF trial demonstrated VNS's efficacy in enhancing functional status and autonomic tone, although cardiac mechanical function showed minimal change. RSD trials, including RDT-PEF and UNLOAD-HFpEF, indicated mixed results with some improvements in symptoms and cardiac function, though limitations like sample size and device effectiveness persist. BAT, through the BAROSTIM NEO System, has shown promise in reducing sympathetic activity and improving heart failure symptoms. The GSN ablation trials indicated significant reductions in pulmonary capillary wedge pressure (PCWP) and improved exercise capacity, though further large-scale studies are needed to confirm these findings.

Neuromodulation-based device interventions represent a promising frontier in HFpEF management, offering potential improvements in symptoms, QoL, and functional status. However, the variability in trial outcomes and the need for further research underscore the necessity for continued investigation to fully establish the efficacy and safety of these therapies.