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Atrial shunt device does not improve outcomes in HFpEF

The Lancet
Reuters Health - 14/02/2022 - Placing an atrial shunt device does not appear to reduce heart failure rates or improve the health of patients with heart failure and ejection fraction of 40% or higher, a large industry-sponsored randomized controlled trial finds.

"In patients with heart failure and preserved ejection fraction (HFpEF), treatment with an atrial shunt device, which is able to dynamically decompress the overloaded left atrium and reduce left atrial pressure, did not improve health status or reduce heart failure hospitalizations overall," lead study author and principal investigator Dr. Sanjiv J. Shah of Northwestern University Feinberg School of Medicine in Chicago, Illinois, told Reuters Health by email.

"However, pre-specified and post-hoc subgroup analyses demonstrated that patients with evidence of dynamic pulmonary vascular disease during exercise did worse with the device, whereas those who had normal pulmonary vascular function during exercise did better with the device," he added.

To investigate whether the Corvia Interatrial Shunt Device System II improves outcomes in heart failure patients, Dr. Shah and his colleagues conducted the phase 3 REDUCE LAP-HF II pivotal trial of the device - a self-expanding nitinol cage with double-disk design and 8-mm-diameter opening in its center - at 89 healthcare centers in the United States, Canada, Europe, Australia, and Japan.

REDUCE LAP-HF II followed the REDUCE LAP-HF I multicenter study in which Dr. Shah and his team found no significant differences at 12 months in rates of all-cause death or major adverse cardiovascular events between 22 patients who received the device and those who received a sham procedure (https://bit.ly/33o69AU).

Over about three years, the researchers enrolled 1,072 participants in REDUCE LAP-HF II. Patients were over 40 years of age (median 72; 62% female), with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Of these, 314 received the atrial shunt device and 312 received a sham procedure. Patients and outcome evaluators were masked to the randomization.

Patients who received the device underwent imaging of the interatrial septum by intracardiac or transesophageal echocardiography, followed by placement of the device in the interatrial septum with fluoroscopic guidance through the femoral vein. Those who received the sham procedure also underwent femoral venous puncture with sheath placement and imaging of the interatrial septum. Participants were followed up at 1, 3, 6, 12, and 24 months, then yearly, for a total of 5 years.

The hierarchical composite primary endpoint included change in health status according to the overall summary score on the Kansas City Cardiomyopathy Questionnaire at 12 months, cardiovascular death or non-fatal ischemic stroke at 12 months, and total heart failure rate up to 24 months.

As reported in The Lancet, the researchers found no differences between the two groups in either the primary composite endpoint (win ratio 1.0; p=0.85) or in the primary endpoint's individual components. They also found no differences in the composite safety endpoint between the two groups (p=0.11).

In prespecified subgroup analyses, patients who had more frequent heart failure when treated with the device tended to be male, have pulmonary artery systolic pressure above 70 mm Hg at 20 watts of bicycle exercise, and have right atrial volume index at or above 29.7 mL/m2.

"HFpEF is considered one of the largest unmet needs in cardiovascular medicine today," Dr. Shah said. "Over 3 million patients have HFpEF, and only one therapy - SGLT2 (sodium-glucose cotransporter-2) inhibitors - has ever been successful for HFpEF in clinical trials. But despite SGLT2 inhibitors, patients still have high morbidity and mortality."

"The results of our trial move us one step closer to a future of precision medicine therapeutics in HFpEF. Although the overall trial was neutral, we identified a potential responder group (two-thirds of patients enrolled in the study) who may benefit from the device," he noted.

Dr. Sean P. Pinney, a professor of medicine and the director of Advanced Heart Failure, Transplant and Mechanical Circulatory Support at University of Chicago Medicine, said in an email, "We desperately need clinical studies in HFpEF."

"We need to keep investigating innovative therapies to help HFpEF patients," said Dr. Pinney, who disclosed that he was involved with the trial at a former institution, but is not an author on the current study. "We learn with each of these trials how important it is to clinically phenotype HFpEF patients and tailor therapies to target their particular pathophysiology."

In an accompanying editorial, Drs. Navin K. Kapur, Jenica N. Upshaw, and Benjamin S. Wessler of Tufts Medical Center in Boston, Massachusetts, write: "Although the findings of the REDUCE LAP-HF II trial are neutral, the authors have generated novel and necessary insight to advance the field by potentially answering pertinent questions, such as do women respond differently than men (and why)? What are the optimal haemodynamic criteria (such as pulmonary vascular resistance values or right-to-left pressure gradients) to study? And, what is the best assessment to exclude significant right heart failure?"

Corvia Medical funded the study, and the results were presented on February 1, 2022 at the Technology and Heart Failure Therapeutics (THT) 2022 conference held live in New York City and virtually.

SOURCE: https://bit.ly/3sAG89Y and https://bit.ly/366PjYg The Lancet, online February 1, 2022.

By Lorraine L. Janeczko

© 2023 The Author(s). Published by Medicom Medical Publishers.
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