Atrial shunt fails to improve outcomes vs. sham in HFpEF: REDUCE LAP-HF II trial
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Placement of an atrial shunt device failed to reduce the rate of HF events or improve health status vs. sham in patients with HF with preserved ejection fraction, according to results of the REDUCE LAP-HF II trial published in The Lancet.
“Dyspnea due to left atrial pressure overload during exercise is a hallmark of heart failure with preserved or mildly reduced ejection fraction,” Sanjiv J. Shah, MD, professor of medicine and director of the T1 Center for Cardiovascular Therapeutics at Northwestern University Feinberg School of Medicine, and colleagues wrote. “The potential therapeutic benefit of an iatrogenic interatrial shunt in heart failure is based on the observation that the presence of a congenital secundum atrial septal defect in patients with mitral stenosis (Lutembacher syndrome) appeared to be beneficial due to the ability to decompress the pressure-overloaded left atrium by shunting blood to the lower pressure reservoir of the right atrium and systemic veins.”
The REDUCE LAP-HF II trial
REDUCE LAP-HF I, the predecessor of the present study, was a randomized multicenter study of 44 patients (mean age, 70 years; 50% women) with class III HFpEF who were randomly assigned to the transcatheter interatrial shunt device (IASD, Corvia Medical) compared with sham procedure. Efficacy of the shunt device was assessed by pulmonary capillary wedge pressure during exercise at 1 month, and safety was assessed by the number of adverse cardiac, cerebrovascular and renal events.
As Healio previously reported, the shunt device reduced exercise pulmonary capillary and peak pulmonary capillary wedge pressure compared with the sham procedure without compromising safety.
The phase 3, randomized, double-blind, sham-controlled REDUCE LAP-HF II trial was designed to determine whether the shunt device would improve outcomes and quality of life, the researchers wrote.
For the present analysis, researchers randomly assigned 626 patients with symptomatic HF, EF 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 (median age, 72 years; 62% women), to either the atrial shunt device or sham procedure from May 25, 2017, and July 24, 2020. The primary endpoint was a composite of CV death or nonfatal ischemic stroke at 12 months, rate of total HF events up to 24 months and change in Kansas City Cardiomyopathy Questionnaire score at 12 months. Researchers also conducted a prespecified subgroup analysis for the HF event endpoint alone.
Results of REDUCE LAP-HF II
According to the study, the primary endpoint did not differ between patients who underwent the shunt procedure compared with the sham procedure (win ratio = 1; 95% CI, 0.8-1.2; P = .85), nor the individual components of the primary endpoint.
In the prespecified subgroup analyses, researchers observed worse HF event outcomes among patients who received the shunt device who were men (P for interaction = .02), had elevated right atrial volume index (P for interaction = .012) and had pulmonary artery systolic pressure of more than 70 mm Hg at 20 W exercise (P for interaction = 002).
A composite safety endpoint consisting of a variety of adverse events did not differ between the groups (shunt group, 38%; sham group, 31%; P = .11).
“In this adequately powered, sham-controlled, randomized trial ... placement of an atrial shunt device did not result in a reduction in total rate of heart failure events or improvement in health status,” the researchers wrote. “Additional studies will be required to evaluate the efficacy, safety, durability and long-term clinical impact of atrial shunt device treatment in patients with heart failure and ejection fraction of at least 40% with no evidence of pulmonary vascular disease during exercise.”
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