ATLANTA — Interatrial shunts failed to provide clinical benefit to heart failure (HF) patients across the RELIEVE-HF trial, but actual harms and benefits depend on patients’ left ventricular ejection fraction (LVEF). It seems that it will be done.

For well-treated patients who are refractory to standard medications, Ventura interatrial shunts are associated with near-total mortality, defined by a hierarchical composite endpoint counting all-cause death, heart transplantation or left ventricular assist device implantation, and heart failure. It was comparable to sham treatment in terms of primary efficacy over 2 years. hospitalization, worsening of outpatient heart failure events, and change in Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS) of 5 points or more. In this ranked analysis, the weighted device win rate over placebo for the interim analysis was 0.86, which was not significant (P=0.20).

The primary safety endpoint for RELIEVE-HF was a device- or procedure-related serious adverse event at 30 days, with a confidence interval of 0%, well below the 11% performance goal. Ta (P<0.0001).

“Transcatheter implantation of the Ventura interatrial shunt was safe but did not reduce symptoms or improve 2-year prognosis in patients with heart failure across the entire LVEF range,” said Greg Stone, M.D., of Mount Sinai Hospital in New York City. There was nothing to do.” , at the American College of Cardiology (ACC) Annual Meeting.

Upon further examination, a prespecified stratified analysis suggested that interatrial shunt implantation was beneficial in patients with reduced LVEF and detrimental in patients with preserved LVEF.

Dr. Stone found that people with LVEF >40% lose disproportionately more in stratified endpoints if they receive a shunt (win rate 0.61, CI 0.39-0.98), whereas the group with LVEF ≤40% loses disproportionately more in stratified endpoints if they receive a shunt. reported that it supported neither benefits nor harm. Event curve analysis showed that cardiovascular events were reduced in shunt patients when LVEF was 40% or less (49.0% vs. 88.6% per year; P<0.0001)、ただし LVEF が >40% had an increase in events (60.2% vs. 35.9% per year; P=0.0001). Most deaths in the LVEF preservation group were ruled to be HF-related or sudden.

So while shunt therapy is “potentially a very good treatment” for patients with HFrEF, “we would be very cautious” about shunt therapy in patients with HF with preserved ejection fraction (HFpEF), Stone said. he said. Mechanistically, this suggests that the higher compliance of the heart in people with reduced LVEF, in contrast to the relatively lower compliance of ventricles with preserved LVEF, is better suited to the more blood flow generated by the shunt. Endurance might explain it, he added.

Based on this, Mary Nolin Walsh, M.D., of Ascension St. Vincent Hospital in Indianapolis, highlighted the question of when shunt therapy fits into the course of a HF patient. She commented that some people with LVEF >40% likely had HFrEF at some point and recovered to some extent.

“How long will we have to wait after GDMT? [guideline-directed medical therapy] Before we think about this, things will get even more intense and when will it be too late and we will be in harm’s way? ” she asked at the ACC press conference.

Stone acknowledged that these findings should be considered exploratory because the LVEF subgroup analysis did not independently strengthen the validity.

In theory, interatrial shunts should provide an autoregulatory mechanism to reduce left atrial pressure and improve heart failure symptoms. The device tested in RELIEVE-HF, the Ventura shunt, has an hourglass shape that fits into the fossa ovalis between the right and left atria. It has a nitinol frame and is inserted using a 14-F delivery system.

Stone cited pilot studies showing that shunts lowered filling pressures and improved heart structure and function, leading to symptom relief and improved function in HFrEF and HFpEF.

Going forward, he predicted, based on current knowledge, shunt trials will focus on patients with reduced LVEF. He noted that further research is needed to elucidate the pathogenesis of this disease, which responds better to shunt therapy with preserved LVEF.

Another device, the Alleviant system, was tested in the ALLAY-HF pivotal trial in people with an LVEF of at least 40% after early data suggested the benefit of inserting a left-to-right shunt into the atrial septum. Tested.

In the previous REDUCE LAP-HF II trial, another shunt device, Corvia, failed to reduce HF events or improve health status in patients with LVEF ≥40%.

The RELIEVE-HF study was a double-blind study in symptomatic HF patients with LVEF. Subjects were already receiving heart failure treatment with maximally tolerated class I GDMT and a cardiac rhythm management device. Participants also had to have had a hospitalization for HF or an elevated BNP/NT-proBNP result within the past 12 months.

The study authors excluded people with anatomic abnormalities that would preclude implantation of a Ventura interatrial shunt, or with hemodynamic, heart rhythm, or respiratory instability.

Researchers screened 1,136 patients from 11 countries and enrolled 605. Ultimately, 508 patients were randomized 1:1 to interatrial shunt or sham surgery. The intervention group received dual antiplatelet therapy for 6 months after the procedure.

The median age of this cohort was 74 years, and over 60% were male. Nearly 55% had non-ischemic cardiomyopathy rather than ischemic cardiomyopathy. More than 95% were New York Heart Association Class III. Almost half of the participants had an existing implantable cardioverter defibrillator or cardiac resynchronization therapy defibrillator implanted.

Follow-up lasted a median of 22 months, during which time the shunt and sham groups shared similar changes in KCCQ-OS over time. This is evidence of the placebo effect of any treatment on quality of life.