Novel Denervation Tx May Correct Fluid Imbalance in HFpEF

The feasibility of permanent nerve ablation as treatment for heart failure with preserved ejection fraction (HFpEF) was supported by a small first-in-human study.

Eleven patients who received right-sided greater splanchnic nerve (GSN) radiofrequency ablation showed short-term improvements in quality of life and other metrics:

• New York Heart Association (NYHA) class from an average 2.5 at baseline to 2.0 at 1 month to 1.9 at 3 months (both P<0.05)
• Kansas City Cardiomyopathy Questionnaire Overall Summary Score from an average 43 to 65 at 1 month (P<0.05) to 79 at 3 months (P<0.01)
• Heart failure severity (NTproBNP): 1,292 pg/mL to 627 pg/mL at 3 months (P<0.05)

The novel transcatheter venous-based approach was associated with two procedure-related events within 1 month: bradycardia due to anesthesia and a large acute decrease in eGFR that returned to baseline, according to Sanjiv Shah, MD, of Northwestern University Feinberg School of Medicine in Chicago. His report was presented at this year’s virtual conference of the Heart Failure Society of America.

Expected adverse events related to the catheterization procedure were one case each of access site hematoma, access site pain, and right intercostal pain. There were no device-related adverse cardiac events or any unanticipated adverse device effects.

In a previous unpublished study, surgical ablation of the GSN was durable through 12 months of follow-up in HFpEF patients, according to Shah.

“Right-sided GSN ablation is a promising therapy for patients with HFpEF,” he concluded, calling this an “easy-to-perform interventional procedure.”

Elevated pulmonary capillary wedge pressure (PCWP) is a major underlying pathophysiology common to all HFpEF patients, Shah said. The excess blood volume resulting in high exercise PCWP may be due to splanchnic sympathetic nerve activity, which distributes blood from the splanchnic vascular bed into the central venous and arterial system.

As such, blocking the GSN could theoretically improve a heart failure patient’s hemodynamic control and help avoid acute decompensations.

Preliminary tests have also suggested promise for temporary splanchnic nerve block methods such as percutaneous ropivacaine or lidocaine administration.

Ultimately, the best way to denervate or block a splanchnic nerve is unclear, said session discussant Margaret Redfield, MD, of the Mayo Clinic in Rochester, Minnesota.

As for the catheter-based approach tested by Shah’s group, she said that “one could postulate that this has the potential to decrease heart failure hospitalization or increase survival. But if it is safe and at least improves exertional dyspnea, that’s an incredibly important endpoint to meet in these patients who are desperate for something to make them feel better.”

Shah and colleagues included 11 HFpEF patients (eight women, average age 70 years) in the first-in-human study of nerve ablation with the Satera system from Axon Therapies.

Eligibility criteria included NYHA class II/III, left ventricular ejection fraction ≥50%, and high baseline PCWP at rest or with exercise.

Procedural success was achieved in all patients, who were all discharged from the hospital the day after the procedure in February and March of this year.

“This therapy, with more data, may turn out to be an effective therapy for all different HFpEF phenotypes. However, if not, the option for temporary splanchnic nerve blockade could be used to see if there was an acute hemodynamic effect,” Redfield suggested. “Those responders could be randomized to denervation versus sham procedure in future trials.”

The study was inherently limited by the small sample and uncontrolled design. Shah also noted that the study was performed at a single center in Tbilisi, Georgia.

A sham-controlled phase II randomized trial, REBALANCE HF, is planned to enroll HFpEF patients starting January 2021.

“Unfortunately, it’s been incredibly difficult to find a medical therapy that will improve the perturbations that we know are present in HFpEF in the myocardium,” Redfield lamented.

Investigational strategies such as atrial shunting, pericardiectomy, and splanchnic denervation “all have the potential to improve hemodynamics, even though they don’t really modify the myocardium, and are certainly worthy of continued study,” she said.

Last Updated October 07, 2020