It’s still early days for a potential transcatheter technique that tones down sympathetic activation mediating blood volume shifts to the heart and lungs. Such volume transfers can contribute to congestion and acute decompensation in some patients with heart failure. But a randomized trial with negative overall results still may have moved the novel procedure a modest step forward.
The procedure, right-sided splanchnic-nerve ablation for volume management (SAVM), failed to show significant effects on hemodynamics, exercise capacity, natriuretic peptides, or quality of life in a trial covering a broad population of patients with heart failure with preserved ejection fraction (HFpEF).
The study, called REBALANCE-HF, compared ablation of the right greater splanchnic nerve with a sham version of the procedure for any effects on hemodynamic or functional outcomes.
Among such “potential responders,” those undergoing SAVM trended better than patients receiving the sham procedure with respect to hemodynamic, functional, natriuretic peptide, and quality of life endpoints.
The potential predictors of SAVM success included elevated or preserved cardiac output and pulse pressure with exercise or on standing up; appropriate heart-rate exercise responses; and little or no echocardiographic evidence of diastolic dysfunction.
The panel of features might potentially identify patients more likely to respond to the procedure and perhaps sharpen entry criteria in future clinical trials, Marat Fudim, MD, MHS, Duke University Medical Center, Durham, N.C., said in an interview.
Dr. Fudim presented the REBALANCE-HF findings at the annual meeting of the Heart Failure Society of America.
How SAVM works
Sympathetic activation can lead to acute or chronic constriction of vessels in the splanchnic bed within the upper and lower abdomen, one of the body’s largest blood reservoirs, Dr. Fudim explained. Resulting volume shifts to the general circulation, and therefore the heart and lungs, are a normal exercise response that, in HF, can fall out of balance and excessively raise cardiac filling pressure.
Lessened sympathetic tone after unilateral GNS ablation can promote splanchnic venous dilation that reduces intrathoracic blood volume, potentially averting congestion, and decompensation, observed Kavita Sharma, MD, invited discussant for Dr. Fudim’s presentation.
The trial’s potential-responder cohort “seemed able to augment cardiac output in response to stress” and to “maintain or augment their orthostatic pulse pressure,” more effectively than the other participants, said Dr. Sharma, of Johns Hopkins University, Baltimore.
Although the trial was overall negative for 1-month change in pulmonary capillary wedge pressure (PCWP), the primary efficacy endpoint, Dr. Sharma said, it confirmed SAVM as a safe procedure in HFpEF and “ensured its replicability and technical success.”
Future studies should explore ways to characterize unlikely SAVM responders, she proposed. “I would argue these patients are probably more important than even the responders.”
Yet it’s unknown why, for example, cardiac output wouldn’t increase with exercise in a patient with HFpEF. “Is it related to preload insufficiency, right ventricular failure, atrial myopathy, perhaps more restrictive physiology, chronotropic incompetence, or medications – or a combination of the above?”
REBALANCE-HF assigned 90 patients with HFpEF to either the active or sham SAVM groups, 44 and 46 patients, respectively. To be eligible, patients were stable on HF meds and had either elevated natriuretic peptides or, within the past year, at least one HF hospitalization or escalation of intravenous diuretics for worsening HF.
The active and sham control groups fared similarly for the primary PCWP endpoint and for the secondary endpoints of Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score, 6-minute walk distance (6MWD), and natriuretic peptide levels at 6 and 12 months.