Overall Effectiveness of Atrial Shunt for HFpEF Remains Questionable

In a trial that investigated the effectiveness of atrial shunt placement on exercise capacity among individuals with heart failure with preserved ejection fraction (HFpEF), only study participants with no evidence of pulmonary vascular disease were shown to benefit from device placement. Participants with elevated pulmonary vascular resistance (PVR) had inferior benefits.

Findings were published online today in The Lancet.

“HFpEF makes up half of all heart failure cases, yet we have very limited treatment options,” said Sanjiv Shah, MD, director of research at the Bluhm Cardiovascular Institute, director of the Northwestern Medicine HFpEF Program, and first study author, in a statement. “Most standard therapies for heart failure are ineffective in this condition, leaving a major unmet need for a large patient population.”

Among the 1072 persons enrolled in the Corvia REDUCE LAP-HF II pivotal trial between May 25, 2017, and July 24, 2020, from 89 medical centers in the United States, Canada, Europe, Australia, and Japan, 58% (n = 626) were randomized 1:1 to treatment with the atrial shunt device (the study group) or a sham procedure (the control group). They were also stratified by age (< 75 years and > 75 years).

Already known to reduce exercise-induced pulmonary capillary wedge pressure (PCWP) resulting from HFpEF, the team wanted to see the device’s potential for reducing heart failure events and improving patient health status.

Three outcomes comprised their primary endpoint: cardiovascular death or nonfatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score at 12 months.

No difference was seen between the study and control groups for the primary end point (win ratio, 1.0; 95% CI, 0.8-1.2; P = .85). However, subgroup analyses did highlight a possible link between 3 preexisting factors and lack of benefit, or worsened health outcomes, from the atrial shunt device:

• Elevated pulmonary artery systolic pressure (> 70 mm Hg) at 20 W of exercise on a stationary bike (P_interaction = .002)
• Elevated right atrial volume index (> 29.7 mL/m²) (P_interaction = .012)
• Male sex (P_interaction = .02)

For the composite safety end point—cardiovascular mortality, nonfatal ischemic stroke, new-onset or worsening kidney dysfunction, major cardiac events, thrombo-embolic complications, newly acquired persistent or permanent atrial fibrillation or atrial flutter, and ≥30% increase in right ventricular size or ≥30% decrease in tricuspid annular plane systolic excursion—again there were no differences, at 38% in the study group and 31% in the control group (P = .11).

Potential participants were excluded from the study if they had heart failure with reduced ejection fraction (< 30%) and history of stroke, transient ischemic attack, deep vein thrombosis, or pulmonary embolism in the previous 6 months. Ejection fraction for enrollees was confirmed via echocardiography and invasive exercise hemodynamic testing before randomization.

At baseline, the median (interquartile range) Meta-Analysis Global Group in Chronic Heart Failure mortality risk score was 23 (18-26), the median KCCQ overall summary score was 45.8 (29.2-62.5), and one-third of patients had a resting PCWP below 15 mm Hg.

Additional findings over a median follow-up of 691 (389-809) days revealed the following:

• 0.28 heart failure events in the study group vs 0.25 in the control group
• KCCQ score median improvement of 10.2 (–1.8 to 26.8) in the study group vs 9.4 (–2.1 to 22.9) in the control group
• New York Heart Association functional class median improvement of –0.5 (–1.0 to 0.0) in the study group vs 0.0 (–1.0 to 0.0) in the control group
• Fewer heart failure events during the COVID-19 pandemic vs before: 0.19 vs 0.38 per patient-year, respectively
• Superior outcomes from the atrial shunt among patients with a peak exercise PVR < 1.74 Wood units vs > 1.74 Wood units in the form of fewer overall heart failure events (0.71 vs 2.48) and greater change in KCCQ overall summary score (+5.5 vs –6.2)
• Greater incidence of a major cardiac event in the study vs the control group: 4% vs 1%

Despite their evidence pointing to an overall neutral effect of the atrial shunt device, the authors says their findings still add to knowledge of improving outcomes among patients with HFpEF. The data “highlight a potentially important exclusion criterion for interatrial shunt device treatment—pulmonary vascular disease uncovered during exercise,” they noted.

In addition, the device has potential to be a subsequent treatment option among patients on sodium-glucose cotransporter-2 inhibitors whose fluid overload is adequately managed. “Once this occurs, it is unclear whether these drugs provide further benefit,” they wrote. “Further diuresis or treatment with neurohormonal modulators might be counterproductive. Thus, a treatment such as the atrial shunt device might be particularly beneficial in patients already on these medications.”

Ultimately, to determine the long-term effectiveness of atrial shunt devices, long-term studies need to investigate their efficacy, safety, durability, and clinical impact in patients with HFpEF but not comorbid peripheral vascular disease during exercise, the authors concluded.

Reference

Shah SJ, Borlaug BA, Chung ES, et al. Atrial shunt device for heart failure with preserved and mildly reduced ejection fraction (REDUCE LAP-HF II): a randomised, multicentre, blinded, sham-controlled trial. Lancet. Published online February 1, 2022. doi:10.1016/S0140-6736(22)00108-8