Paradigm-Challenging Heart Failure Treatment Strategy Hopeful in Early Trial

May 24, 2022

A small group of patients with heart failure (HF) who underwent a novel transcatheter nerve-ablation procedure seemed to benefit with improved hemodynamics, symptoms, and quality of life in an admittedly limited observational series.

All had HF with preserved ejection fraction (HFpEF) and remained on guideline-directed medical therapy during the study.

The open-label experience has launched a randomized trial, featuring a sham control group, that could ultimately challenge dogma about volume overload in patients with chronic and acute HF and the perceived essential role of diuretics.

Researchers see transvenous ablation of the right greater splanchnic nerve (GSN) as potentially appropriate for patients with HF, regardless of ventricular function or acuity. But the ongoing REBALANCE-HF trial aims to enroll up to 80 patients with chronic HFpEF.

Meanwhile, the current 18 patients with elevated resting or exertional pulmonary capillary wedge pressure (PCWP), given the procedure as part of the main trial's "roll-in" phase, showed declines in exercise PCWP after 1 month (= .007) and improved quality-of-life scores at both 1 and 3 months (P < .01). Also at 1 month, a third of the patients improved by at least one step in NYHA functional class.

The procedure, called splanchnic ablation for volume management (SAVM), could potentially be used "across the spectrum of acute and chronic heart failure, maybe even with reduced ejection fraction (HFrEF) and preserved ejection fraction," Marat Fudim, MD, MHS, Duke University Medical Center Durham, North Carolina, told theheart.org | Medscape Cardiology.

However, "for outcomes, we've really only looked in the ambulatory setting," and only at symptomatic and functional responses. To that extent, based on the current experience and a few small previous studies, Fudim said, SAVM seems to benefit patients with HF in general who have dyspnea at exercise. Beyond that, the kind of patient who may be most suitable for it "is something I hope we will be able answer once the randomized dataset is in."

Fudim reported the REBALANCE-HF roll-in results May 22 at the Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022 sessions, held virtually and live in Madrid. He is also lead author on the same-day publication in the European Journal of Heart Failure.

A Different Treatment Paradigm

Splanchnic-nerve blockade as a possible HF treatment is based on growing evidence that volume overload in patients with HF is not always the cause, at least not a main cause, of congestion and dyspnea. Rather, those classic HF signs and symptoms may often be triggered by adverse redistribution of stable fluid volume from primarily the splanchnic vascular compartment to the intrathoracic space.

In other words, what might seem like classic volume overload calling for diuresis often might actually be euvolemic redistribution of fluid from the abdomen to the chest, raising intracardiac pressures and causing dyspnea.

In that scenario, loop diuretics might only dehydrate the patient and potentially put the kidneys at risk, Fudim proposed. His recent experience with HF patients implanted with a pulmonary-artery pressure monitor, he said, suggests many who received standard volume-overload therapy had actually been normo- or hypovolemic.

More then half the patients "did not have high volume, they just had high pressures," he said. "So there is a significant portion of the population that has pathological processes leading to high pressures, but it's not volume overload. Diuresing those patients would probably not be the right decision."

The unilateral SAVM procedure appears to attenuate sympathetically mediated splanchnic volume redistribution to the heart and lungs, but as it doesn't affect the left GSN, preserves some normal sympathetic response.

Sometimes in studies of surgical or catheter-based SAVM, Fudim said, "we have observationally seen that people discontinued diuretics or decreased doses in the treatment arm."

"Beyond Our Classical Thinking"

It's "impressive" that such right-GSN ablation seemed to reduce exercise-filling pressures, but one should be circumspect because "it's way beyond our classical thinking," Wilfried Mullens MD, PhD, Hospital Oost-Limburg, Genk, Belgium, said as a panelist after Fudim's presentation.

"These are invasive procedures," he noted, "and our physiological understanding does not always match up with what we're doing in real life if you look at other interventional procedures, like renal denervation, which showed neutral effects, or if you look at even interatrial shunt devices, which might even be dangerous."

The field should be "very prudent" before using SAVM in practice, which shouldn't be "before we have sufficient data to support the efficacy and safety," Mullens said. "It remains to be seen how treatment success will be defined. Is it during exercise? How long does the treatment last? What is the effect of the treatment over time; is it not harmful? These are things that we don't know yet."

The procedure was considered successful in all 18 patients, 14 of whom were women and 16 of whom were in NYHA class 3. Their average age was 75 and their mean left ventricular ejection fraction (LVEF) at baseline was 61%. The primary efficacy endpoints were a reduction in PCWP at rest, with legs raised, and at 20W exercise at 1 month. Their baseline invasively measured peak exercise PCWP was at least 25 mm Hg.

At 1 month, mean PCWP at 20W exercise fell from 36.4 mm Hg to 28.9 mm Hg (= .007) and peak PCWP declined from 39.5 mm Hg to 31.9 mm Hg (P = .013); resting PCWP wasn't significantly affected. Twelve patients improved by at least one NYHA functional class (= .02).

Scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), which assesses quality of life, improved by 22 points at 1 month and 18.3 points at 3 months (P < .01 for both differences).

No significant effects on 6-minute walk distance or natriuretic peptide levels were observed, nor were any observed on LVEF or echocardiographic measures of diastolic function, left ventricular (LV) atrial volume, or LV mass at 3 months.

Three "nonserious" device-related adverse events were observed, including one case of acute decompensation early in the experience, ostensibly due to excessive saline administration, Fudim reported. There was also one case of transient periprocedural hypertension and one instance of postprocedure back pain.

The SAVM procedure is performed transvenously, and in general is technically "really not that challenging," Fudim said. In most cases, the necessary skills would be accessible not only to interventional cardiologists but also heart failure specialists. "I have performed this procedure myself, and I'm a heart failure guy."

The REBALANCE-HF roll-in phase and main trial are supported by Axon Therapies. Fudim discloses receiving support from Bayer, Bodyport, and BTG Specialty Pharmaceuticals; and consulting fees from Abbott, Audicor, Axon Therapies, Bodyguide, Bodyport, Boston Scientific, CVRx, Daxor, Edwards LifeSciences, Feldschuh Foundation, Fire1, Gradient, Intershunt, NXT Biomedical, Pharmacosmos, PreHealth, Splendo, Vironix, Viscardia, and Zoll. Mullens discloses receiving fees for speaking from Medtronic, Abbott, Novartis, Boston Scientific, AstraZeneca, and Boehringer Ingelheim.

Heart Failure Association of the European Society of Cardiology (HFA-ESC) 2022. REBALANCE-HF Roll In Cohort. Presented May 22, 2022.

Eur J Heart Fail. Published online May 22, 2022. Abstract

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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