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Atrial shunt placement failed to reduce heart failure events or improve health status in the overall trial, but results suggest a subgroup of patients with a normal response on an exercise test could stand to benefit from the therapy.
A trial examining the use of an interatrial shunt device in patients with heart failure and preserved or mildly reduced ejection fraction has returned mixed results.
Although the trial results demonstrate placement of an atrial shunt did not reduce the total rate of heart failure events or improve health status in patients with HFpEF versus sham therapy, investigators noted further analysis outlined subgroups of patients who may benefit from atrial shunt placement.
“While the overall trial was neutral, in our subgroup analyses, we found that what happens in the heart and lungs during exercise is of prime importance in this type of heart failure,” said principal investigator Sanjiv Shah, MD, director of research at the Bluhm Cardiovascular Institute and director of the Northwestern Medicine HFpEF Program, in a statement. “The normal response to exercise is relaxation of the blood vessels in the lungs. Patients with HFpEF who are able to relax the blood vessels in their lungs appear to do well with the device, whereas those whose blood vessels can’t relax appear to do worse when an atrial shunt is implanted.”
A randomized, international, blinded, sham-controlled trial conducted in 89 medical centers across 4 continents, REDUCE LAP-HF II was designed to assess the effects of shunt device placement on outcomes among patients with symptomatic HFpEF. For inclusion in the trial, patients needed to be at least 40 years of age or older, have an ejection fraction of at least 40%, and a pulmonary capillary wedge pressure during exercise of at least 25 mmHg while exceeding right atrial pressure by at least 5 mmHg.
These patients were randomized in a 1:1 ratio to the shunt device or sham procedure. The primary outcome of interest for the trial was a hierarchical composite of cardiovascular death or nonfatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in KCCQ-OS at 12 months. Investigators noted analyses of the primary outcome and safety outcomes were conducted in the modified intention-to-treat population, which was defined as all patients randomly allocated to receive treatment.
From May 25, 2017-July 24, 2020, 1071 participants were enrolled in the trial and 626 underwent randomization, with 314 randomized to the shunt device and 312 randomized to undergo the sham procedure. Results of the investigators’ analyses indicated there were no between-group differences in the primary composite outcome (Win Ratio, 1.0 [955 CI< 0.8-1.2]; P=.85) or among the individual components of the composite outcome.
Investigators noted prespecified subgroup analyses demonstrated a differential effect of atrial shunt placement on heart failure events pulmonary artery systolic pressure at 20W of exercise (P for interaction=.002 [>70 mmHg associated with worse outcomes]), right atrial volume index of (P interaction=.012 [≥29.7 mL/m2, worse outcomes]), and sex (P for interaction=.02 [men, worse outcomes]). In safety analyses, results suggested there were no difference in the composite safety endpoint between the groups, with events occurring among 38% of patients randomized to shunt device and 31% randomized to sham procedure (P=.11).
“What we saw in this study is encouraging and suggests that future clinical trials should specifically investigate the subgroup of patients with HFpEF whose pulmonary blood vessels respond normally to exercise,” Shah added. “If future trials validate what we found, the potential is enormous. This subgroup comprises two-thirds of people with this type of heart failure – that is 2 million people could benefit from this innovative therapy. This simple, one-time procedure could reduce hospitalizations and significantly improve quality of life.”
This study, “Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial,” was published in The Lancet.