CLEVELAND — Splanchnic nerve ablation was safe in heart failure with preserved ejection fraction (HFpEF) and showed some signal of benefit in volume management in the REBALANCE-HF feasibility study.
The treatment showed a nonsignificant trend for lower work index pulmonary capillary wedge pressure (PCWP) with the procedure than with a sham procedure (4-9 mm Hg/W/kg, P=0.3) and longer exercise duration (35 second difference, P=0.1).
No significant differences were seen in change in right atrial or pulmonary artery pressures, quality-of-life scores, functional capacity, or natriuretic peptides between groups, reported Marat Fudim, MD, MPH, of Duke University Health in Durham, North Carolina, presenting at the Heart Failure Society of America (HFSA) meeting.
But the trial showed safety of the procedure and warrants further study, said HFSA session study discussant Kavita Sharma, MD, of Johns Hopkins University in Baltimore.
“Sympathetically mediated splanchnic vasoconstriction results in rapid shifts of the blood from the heart and lungs to the heart and lungs from the abdominal compartment,” she explained. Whereas that’s a normal physiologic response during exercise, “in heart failure, this may result in exaggerated rise in cardiac filling pressures, worsening of symptoms and an increased risk of heart failure decompensation. And this is ultimately the physiologic target in this therapy.”
The study included 90 higher risk patients with heart failure and an ejection fraction of at least 50% and an exercise PCWP of at least 25 mm Hg who were randomized to either right-sided greater splanchnic nerve ablation or a sham procedure with clinical follow-up through 1 year and exercise hemodynamic testing at 1 month.
For the primary safety endpoint at 1 month, the rate of device or procedure related serious adverse events was 7% with the procedure compared with 2% in the sham group. Two of the three cases were due to pain; the third was a case of aspiration during anesthesia.
Medications were twice as likely to be added during follow-up in the sham versus intervention group, and there were substantially more unscheduled visits with medication changes in the sham group as well.
Responder group analysis suggested that the procedure was more effective in those with preserved cardiac output with exercise or standing, with ability to augment heart rate, and with absence of advanced structural disease.
For the 55% of participants with these characteristics, PCWP and exercise duration gains were significant (-18 mm Hg/W/kg and +95 seconds vs sham, respectively, both P=0.02). Quality of life, exercise capacity, and NT-proBNP levels also trended or were statistically significant for the intervention versus sham as well at 12 months.
Further studies are needed to confirm potential benefits in this responder group, Fudim said.
The responder group physiologically “fits” the therapy, agreed Sharma.
Limitations she noted included the discrepancy in female enrollment (55% in the intervention group vs 74% in the sham group), low under-represented minority enrollment, and 11% rate of orthostasis.
Perhaps more important is an understanding of the patients who were not responders — why they were unable to augment cardiac output in HFpEF, Sharma noted.
REBALANCE was supported by Axon Therapies.
Fudim disclosed financial relationships with Axon Therapies.
Sharma disclosed financial relationships with AHA Go Red for Women, Amgen, FNIH HeartShare, Alleviant, Bayer, Bristol Myers Squibb, Boehringer-Ingelheim, Cytokinetics, Edwards LifeSciences, Janssen, Novartis, Novo Nordisk, and RIVUS.
Heart Failure Society of America
Source Reference: Fudim M “Endovascular ablation of the right greater splanchnic nerve in heart failure with preserved ejection fraction: primary results of the REBALANCE-HF randomized trial” HFSA 2023.