麻豆传媒

ATLANTA -- An interatrial shunt failed to provide a clinical benefit to people with heart failure (HF) overall in the RELIEVE-HF trial, though actual harm or benefit seemed to hinge on the patient's left ventricular ejection fraction (LVEF).

For well-treated patients refractory to standard medications, the Ventura interatrial shunt was no better than sham in terms of primary effectiveness over nearly 2 years, defined by a hierarchical composite endpoint counting all-cause death, cardiac transplant or LV assist device implantation, HF hospitalization, outpatient worsening HF events, and 5+ point change in Kansas City Cardiomyopathy Questionnaire overall score (KCCQ-OS). This ranked analysis left the device with a nonsignificant win ratio of 0.86 over placebo, weighted for an interim analysis (P=0.20).

RELIEVE-HF's primary safety endpoint was device- or procedure-related major adverse events at 30 days, which stayed at 0% with the confidence interval well under the performance goal of 11% (P<0.0001).

"Transcatheter implantation of the Ventura inter-atrial shunt was safe but did not reduce symptoms or improve prognosis through 2 years in patients with HF across the full range of all LVEF," reported Gregg Stone, MD, of Mount Sinai Hospital, New York City, at the American College of Cardiology (ACC) annual meeting.

On closer inspection, a pre-specified stratified analysis suggested that inter-atrial shunt implantation was beneficial in patients with reduced LVEF and harmful in patients with preserved LVEF.

Stone reported that people with LVEF >40% had disproportionately more losses in the hierarchical endpoint if they got the shunt (win ratio 0.61, CI 0.39-0.98) while the LVEF ≤40% group did not support either benefit or harm from shunting. By event curve analysis, there were fewer cardiovascular events for shunted patients if LVEF was ≤40% (49.0% vs 88.6% per year, P<0.0001), but more events if LVEF was >40% (60.2% vs 35.9% per year, P=0.0001). Most of the deaths in the preserved LVEF group were adjudicated as HF-related deaths or sudden deaths.

Shunting is therefore a "potentially very good therapy" for patients with HFrEF whereas "I would be very cautious" about shunt therapy in HF with preserved ejection fraction (HFpEF), Stone said. Mechanistically, this might be explained by the more compliant hearts in people with reduced LVEF, which can better tolerate the greater blood flow created by the shunt, in contrast with the relatively noncompliant ventricle in preserved LVEF, he added.

Based on this, Mary Norine Walsh, MD, of Ascension St. Vincent Hospital in Indianapolis, stressed the question of when shunt therapy would fit in the HF patient trajectory. She commented that some people with LVEF >40% likely had HFrEF at some point with some recovery.

"How long would we wait after GDMT [guideline-directed medical therapy] intensification before we would think about this, and when is it too late and we'll be doing harm?" she posed during an ACC press conference.

Stone acknowledged that these findings should be considered exploratory, as the LVEF subgroup analyses were not individually powered for effectiveness.

In theory, an interatrial shunt should provide an autoregulatory mechanism to decrease left atrial pressure and improve HF symptoms. The device tested in RELIEVE-HF, the Ventura shunt, has an hourglass shape that fits across 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 the shunt reduced filling pressures, improved cardiac structure and function, and provided symptomatic relief and functional improvement in HFrEF and HFpEF.

Going forward, he predicted that shunt trials will shift efforts to patients with reduced LVEF based on the present findings. In preserved LVEF, more work is needed to tease out the etiologies in this disease that would better respond to shunt therapy, he noted.

Another device, the Alleviant system, is being tested in the ALLAY-HF pivotal trial in people with LVEFs of at least 40% after early data suggested benefit to putting the left-to-right shunt in the interatrial septum.

Previously, in the , another shunt device, the Corvia, failed to reduce HF events or improve health status in patients with LVEF ≥40%.

The RELIEVE-HF trial was a double-blind study of symptomatic HF patients with any LVEF. Eligible people were already on maximally-tolerated class I GDMT and cardiac rhythm management device therapy for HF. Participants also had to have a HF hospitalization within the prior 12 months or an elevated BNP/NT-proBNP result.

Study authors excluded people who had an anatomical anomaly precluding implantation of the Ventura interatrial shunt and those who had hemodynamic, heart rhythm, or respiratory instability.

The investigators had screened 1,136 patients from 11 countries and enrolled 605. Ultimately, 508 people were randomized 1:1 to the interatrial shunt or a sham procedure. The intervention arm received 6 months of dual antiplatelet therapy after the procedure.

This cohort had a median age of 74 and was over 60% men. Nearly 55% had a nonischemic cardiomyopathy as opposed to an ischemic cardiomyopathy. Over 95% were in New York Heart Association class III. Nearly half of participants had an existing implantable cardioverter-defibrillator or cardiac resynchronization therapy-defibrillator implant.

Follow-up lasted a median 22 months, during which shunt and sham groups shared similar changes in KCCQ-OS over time -- a testament to any procedure's placebo effect on quality of life.

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