Interatrial Shunt Device Shows Sustained Improvement in Heart Failure Patients With Preserved EF

NEW ORLEANS, LA—A novel transcatheter intracardiac shunt device appears to provide sustained clinical benefit at 1 year in heart failure patients with preserved or only mildly reduced ejection fraction, according to new results from the REDUCE-LAP trial.

David Kaye, MD (Alfred Hospital, Melbourne, Australia), who presented the 12-month results here at the American Heart Association Scientific Sessions 2016, reported that shunt patency was preserved at 1 year with no signal of safety issues or adverse events.

“Taken together, the present study shows that implantation of an interatrial shunt device appears to be safe with an acceptable MACCE rate through 1 year of follow-up,” Kaye said. “Randomized trials are required and ongoing to determine the value of this novel strategy for the management of heart failure with preserved ejection fraction.”

To TCTMD, Kaye stressed that this therapy entails a very close collaboration between heart failure specialists and interventional cardiologists.

“I’m a heart failure cardiologist so I work closely with our interventional cardiologists,” he said. “And I think for all of the centers who are in the trial, that’s typically the way they’ve been managing the patients and it’s a good partnership.”

The catheter-based procedure requires femoral vein puncture and catheter crossing of the inter-atrial septum, which he characterized as “pretty routine” for many interventionalists and electrophysiologists. The whole procedure typically takes in the range of 1 hour to perform and can be done under light sedation, rather than general anesthesia, “which is important in an elderly population,” he added.

HFpEF: A Crippling Disease Lacking Solutions

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly 50% of heart failure cases, and its prevalence is increasing. No pharmacological trial to date has managed to show significant mortality reductions in the patients, often elderly, suffering from this disease.

The hallmark finding of HFpEF is elevated pulmonary capillary wedge pressure (PCWP), especially during physical activity. This is linked with both reduced 6-minute walk distance and long-term survival, Kaye said. The hypothesis explored in the open-label REDUCE-LAP trial was whether placement of an interatrial shunt device can lower left atrial pressure by allowing decompression of the right atrium and mitigate pulmonary congestion.

“The stories of an older person not being able to get dressed or walk down to their mail box: these are real stories.” David Kaye

A total of 64 patients (mean age 70) with LVEF 40% or greater and NYHA class II-IV heart failure were enrolled in the study. At 12 months, three patients had died, including one from a stroke. Device effectiveness, defined as left-to-right shunt flow, was 100%, and cardiac outcome showed sustained improvements from baseline. Importantly, no right-to-left shunt was seen. Device patency was confirmed by echocardiography or oximetry in 54 subjects. At 6 months, patients showed significant improvement in NYHA class, Minnesota Living with Heart Failure (MLWHF) Score, and 6-minute walk distance, with all three parameters holding steady between 6 and 12 months.

Device safety was also sustained, Kaye told TCTMD. “You’re allowing blood to come from the left side to load up the right side a little more, so there’s been a concern that that might cause a problem on the right side. That’s one of the big concerns, and we see no signal of that. At 6 months we saw a very small increase, but then that hasn’t changed out to a year now.”

The other concern “which you have with any device in the heart” is stroke risk. One stroke occurred, but this was in a patient with a high stroke risk at baseline, and the overall stroke rate in the trial was no different than what is commonly seen in HFpEF patients, Kaye said. “Pulmonary hypertension is a concern, again, because of more blood flow to the right, but we’ve measured the pressures and there’s no signal there. And the final thing that people have wondered is, would the device close over? And we have very good evidence that the device stays open.”

A randomized, sham-controlled trial of the shunt device is now underway and according to Kaye will likely have results in the first half of 2017.

A Truly Novel Therapy

Discussing the results following Kaye’s presentation, Nancy Sweitzer, MD (University of Arizona, Tucson), congratulated the REDUCE-LAP investigators “for beginning an investigation of a truly novel therapy for this disease.”

She pointed out that certain questions remain unanswered, including rates of rehospitalization in these patients, as well as full evaluation of hemodynamics (independent core lab assessment was only able to assess shunt flow in 49 patients due to poor image quality). She also pointed out that while HFpEF is common, this particular treatment would only be suitable for some patients and just who would be best suited is not yet clear.

Also, given the nonrandomized nature of the study, there remains the potential for a placebo effect.  “Anyone enrolled in a heart failure trial tends to get better,” she noted.

But showing an analysis comparing the improvements in 6-minute walk distance and MLWHF score across a range of heart failure studies of implanted rhythm devices, Sweitzer focused on the degree of improvement in the active versus sham-control arms. She noted that while other device trials have shown a ‘placebo’ effect in control-arm patients, the magnitude of the benefit seen with the shunt-device in REDUCE-LAP is more similar to that of patients in the active arms of these device trials and not the smaller benefit typically seen in sham-treated arms.

“I think this suggests that the magnitude of the improvements seen in HF patients in the REDUCE-LAP trial is provocative and suggests that perhaps this is a real effect and not placebo effect,” she said.

To TCTMD, Kaye said he’s reassured by the 12-month results and “optimistic” about the ongoing randomized trial, and the potential to help an underserved population. “The stories of an older person not being able to get dressed or walk down to their mail box: these are real stories and they are very hard to treat.”

Image screen capture courtesy of the Corvia Medical website.