Testimony to FDA’s Circulatory System Devices Panel regarding the premarket application for the V-Wave Ventura Interatrial Shunt System
By Michael T. Abrams, M.P.H., Ph.D.
I am Michael Abrams, senior health researcher with the nonprofit, consumer advocacy organization Public Citizen. I have no financial conflicts of interest related to today’s topic.
The V-Wave Ventura Interatrial Shunt System is being evaluated by this committee for potential FDA approval as a treatment for symptomatic heart failure that is nonresponsive to guideline therapy and where the left ventricular ejection fraction is less than 40%. Because this device is implanted into the heart via catheterization, it is a class III device, thus requiring the sponsor to demonstrate the highest level of safety and effectiveness evidence before approval is granted.
The FDA briefing document for today’s meeting is largely critical of the sponsor’s premarket application (PMA).[1] That PMA is mostly based upon the sponsor’s updated analysis of its RELIEVE-HF, a randomized controlled trial involving 508 heart failure patients assigned 1:1 to either the shunt installation or a sham procedure. This trial was designed to test the expectation that the V-Wave would offer relief to all heart failure patients, regardless of their ejection fraction.
That prespecified primary therapeutic goal was not achieved. However, post-hoc analyses, which split the sample into those with ejection fraction less than 40% (low ejection fraction) and others, revealed that the shunt was beneficial for the low ejection fraction subgroup. Based on these results, the sponsor now seeks approval of their device.
FDA reviewers, appropriately, have concerns about such analyses driving an approval decision.
Here are some of those concerns:
The subgroup testing was to be performed only if the full-heart-failure-group effectiveness endpoint was met. Accordingly, false-positive results (type 1 errors) are a concern, and the subgroup analyses should be “interpreted with caution”[2] and considered as “hypothesis-generating”[3] and “for descriptive purposes only.”[4] To underscore this fundamental statistical principle, the FDA cited a 2016 paper by Pocock and Stone which says that “we find it hard to think of an example in which an apparent benefit in a subgroup in a trial with a negative outcome has led to a confirmation in a subsequent trial.”[5] The FDA further described at least three cardiovascular trial series (PRAISE, TACT, and PARAGON-HF) that first demonstrated significant subgroup effects but later had to reject those effects because they were not confirmed by a second trial.[6]
The FDA review also noted that the low-ejection-fraction subgroup analysis did not show significant V-Wave benefits on the primary outcome variable, just on a subset.[7] For example, the FDA review said this: “It is important to note that in the HFrEF (low ejection fraction) subgroup, shunt subjects did not experience an improved health status (or) quality of life (status) compared to control subjects.”[8]
Finally, it should be noted that the post-hoc analysis, upon which this application was built, showed that shunt recipients with preserved ejection fraction (>40%) experienced significantly more harm than their matched controls, based on the sponsor’s primary analytic strategy. This unanticipated result exposes plausible risks associated with this device.[9]
One other caution described by the FDA is that ejection fraction measurement (a percent) is subject to error and changes over time due to factors other than treatment, such as the natural evolution of the disease. Accordingly, it is uncertain that a single ejection fraction threshold (40%) can reliably indicate a shunt treatment or otherwise.
Regarding adverse effects of the V-Wave shunt, the FDA noted that major adverse events, such as all-cause death or stroke, were not evident within one month of shunt installation. However, within two years, cerebrovascular or pulmonary risks became apparent with V-Wave shunt use.[10]
These and related points lead to the following conclusion: The benefit-to-risk profile of the V-Wave interatrial shunt for heart failure with reduced ejection fraction remains speculative. Public Citizen urges the committee to recommend that the FDA reject this PMA. Further FDA consideration of the PMA should be contingent on the sponsor conducting a new and appropriately powered clinical trial comparing shunt installation to a sham placebo and that enrolls participants with an ejection fraction less than 40%.
Thank you.
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[1] U.S. Food and Drug Administration. FDA Executive Summary: V-Wave Venture Interatrial Shunt System. Meeting of the Circulatory System Devices Panel. December 3, 2025. https://www.fda.gov/media/189898/download. Accessed December 1, 2025.
[2] Ibid. p. 22
[3] Ibid. p. 21
[4] Ibid. p. 22
[5] Ibid. p. 22
[6] Ibid. pp. 23-24
[7] Ibid. p. 44
[8] Ibid. p. 45
[9] Ibid. p. 55
[10] Ibid. pp. 30-32