Splanchnic nerve ablation effective in HF with preserved ejection fraction, shows first-in-human study.

Recent research has indicated that the underlying pathophysiology for clinical manifestations of heart failure with preserved ejection fraction (HFpEF) is an increased sympathetic tone of capacitance vessels that leads to increased central filling pressures. Researchers Malek et al proposed that ablating sympathetic tone in a large capacitance bed like splanchnic circulation by unilateral splanchnic nerve ablation can serve to ameliorate the symptom of HFpEF by improving the volume redistribution caused by enhanced sympathetic tone in capacitance vessels.

In their study published in the May edition of the European Journal of Heart Failure, they have shown the feasibility of this concept in a first-in-human study of right great splanchnic nerve ablation in patients with HFpEF, which resulted in resting intra-cardiac filling pressures, paired with an improvement in exercise capacity and self-reported symptoms and quality of life.

In a single‐arm, prospective trial, 10 patients with HFpEF (50% male, 70±3 years) all with NYHA class III, left ventricular ejection fraction > 40%, pulmonary capillary wedge pressure (PCWP) ≥ 15 mmHg at rest or ≥ 25 mmHg with supine cycle ergometry, underwent ablation of the right greater splanchnic nerve (GSN) via thoracoscopic surgery.

Patients were evaluated at baseline, 1, 3, 6 and 12 months after the procedure. The primary endpoint was a reduction in exercise PCWP at 3 months. There were no adverse events related to the blockade of the nerve during 12 months follow‐up.

At 3 months post GSN ablation, patients demonstrated a significant reduction in 20 watts exercise PCWP when compared to baseline ‐4.5 mmHg which carried over to peak exercise ‐5 mmHg.

At 12 months improvements were seen in NYHA class and quality of life assessed with the Minnesota Living with Heart Failure Questionnaire.

Exercise intolerance manifested either as exertional dyspnea and/or fatigue is a hallmark of HFpEF. While many mechanisms likely contribute to the limitations in exercise and the ability to perform activities of daily living in HFpEF, there is growing evidence of profoundly abnormal hemodynamic response to exercise characterized by rapid and marked elevation in filling pressures, which typically promptly return to baseline values during recovery. Therefore, recently an inappropriate control of blood volume distribution in the body has been proposed as a mechanism underlying exercise intolerance in HFpEF.

Activation of splanchnic nerves results in vasoconstriction, reduces splanchnic capacitance, therefore recruiting blood volume into central circulation. It is thought that this redistribution of blood volume (caused by sympathetic activation), even if by a relatively small amount, may lead to a sudden rise in pulmonary and left-sided cardiac pressures in HF accounting for dyspnea and exercise intolerance.

Malek et al have developed a novel approach to restore the normal function of the splanchnic vascular reserve in order to relieve resting and exercise induced intra-cardiac pressure elevations that occur in HFpEF. Although further randomised control trials will shed light on the actual benefits of this therapy, this novel first-in human experience has definitely opened exciting avenues for targeted sympatholytic therapy as a treatment modality in HFpEF.

Additionally, given the considerable procedure-related morbidity from a surgical GSN ablation, a catheter-based approach is being developed in order to enable larger trials and provide a less invasive method of GSN ablation.

"We believe that selective ablation of the right greater splanchnic nerve (GSN) in patients with HFpEF, with resultant reduction in the sympathetic nerve traffic to the splanchnic bed, will lead to greater vascular compliance during exercise, lower pulmonary and cardiac filling pressures, and improved exercise tolerance, ultimately leading to improvements in quality of life", concluded the authors.

Source: European Journal of Heart Failure: Málek F, Gajewski P, Zymliński R, Janczak D, et al. Surgical ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction: First-in-human clinical trial. Eur J Heart Fail. 2021 May 1. doi: 10.1002/ejhf.2209.