By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
SYNOPSIS: Placement of an interatrial shunt device in patients with heart failure with preserved or mildly reduced ejection fraction did not lower the rate of heart failure events or improve health status.
SOURCE: 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 2022;Jan 31:S0140-6736(22)00016-2. doi: 10.1016/S0140-6736(22)00016-2. [Online ahead of print].
Despite advances in medical therapy, morbidity from congestive heart failure (CHF) remains high. Clinical experience with naturally occurring interatrial shunts suggests decompression of the left atrium by volume unloading to the low-pressure right atrium and venous system might represent a viable interventional target for therapy. Specifically, the occurrence of congenital atrial septal defects in patients with mitral stenosis carries a well-described protective effect, such that left atrial pressure is shielded from rising in proportion to the severity of stenosis. This well-tolerated combination of defects even has an eponymous name: Lutembacher syndrome.
Based on these observations, devices that create iatrogenic interatrial shunts have been developed and come a relatively long way in the past few years. Currently, at least six shunt devices are in various stages of study. The one with the most data, the Corvia device, is implanted percutaneously by way of a relatively simple procedure via the femoral vein, resulting in a permanent 8 mm opening between the two chambers. The authors of an initial open-label trial, called REDUCE LAP-HF, enrolled CHF patients with elevated pulmonary capillary wedge pressure (PCWP) and left ventricular ejection fraction (EF) ≥ 40%. The device resulted in improved invasive hemodynamics. At one year, those patients reported improvements in New York Heart Association (NYHA) class and quality of life measures without evidence of device-related complications.1
Shah et al reported the results of the larger follow-up trial: REDUCE LAP-HF II. As in the earlier study, patients with HF with preserved or mildly reduced EF were the primary target. Enrolled patients were required to record a PCWP of at least 25 mmHg during exercise, and this had to exceed right atrial pressure by at least 5 mmHg. High resting right atrial pressure was an exclusion, as was high pulmonary vascular resistance, hemodynamically significant valvular disease, or other complications (including stroke, deep vein thrombosis, or pulmonary embolism).
Over the three-year study period, 626 patients were randomized 1:1 to either implantation of the device or to a sham procedure involving femoral vein puncture and imaging of the interatrial septum. A total of 93% of patients had preserved systolic function, with a median EF of 60% in the overall group. Procedure-related events were rare but did occur, with three out of 308 device patients developing cardiac tamponade, and one requiring emergency cardiac surgery.
The primary endpoint was a hierarchical composite of cardiovascular death or stroke at 12 months, rate of heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score at 12 months. This endpoint was not different between the device and sham groups. KCCQ scores improved in both groups at one year to a similar extent. HF events did not differ between treatment groups, although NYHA class improved to a greater degree in the device-treated patients. Prespecified subgroup analyses showed device treatment resulted in worse HF event outcomes in men, in patients with huge right atria, and in patients with significant pulmonary hypertension during exercise. This last observation triggered a post-hoc analysis, the results of which suggested patients with a normal pulmonary vascular response to exercise appeared to benefit from the shunt device. The authors concluded placement of the Corvia atrial shunt device failed to lower the rate of HF events or improve health status in this population of patients with HF and EF > 40%.
COMMENTARY
The neutral result of this trial represents a highly disappointing outcome for both healthcare providers and patients, who had hoped for a clear signal of benefit from this intervention. The perceived promise of such an atrial shunt device is illustrated by the sheer number of devices that are in different stages of testing. Currently, the Corvia device studied here is the farthest along, but clinical trials are also in progress for others.
REDUCE LAP-HF II was well designed and executed, with a level of planning and rigor that speaks to the experience of the organizers. The sham-controlled design was an important inclusion, especially where quality of life scoring is part of the composite primary outcome. Meticulous invasive hemodynamics and exercise testing were used to identify patients who were most likely to benefit (and least likely to be harmed) by an iatrogenic interatrial shunt. Such testing is not routinely conducted outside a relatively small subset of centers. However, even with these strict controls, no significant clinical benefit was seen in the overall group, and some subsets appeared to have experienced net clinical harm from the procedure. The suggestion that some groups may have enjoyed clinical benefit (e.g., patients who maintain normal pulmonary vascular resistance during exercise) is intriguing and provides some direction for future study.
The fact this trial did not demonstrate benefit in such a cherry-picked population strongly suggests the strategy of left atrial decompression via interatrial shunt is unlikely to become a generally applicable therapy for most patients with CHF. The results of this study will help identify even smaller subsets that may benefit from such a device. For now, there is not sufficient evidence of efficacy to allow approval in the United States. We should acknowledge the possibility that alternative device designs may turn out to be more successful in CHF treatment, but that conclusion remains speculative until future trial data are available.
REFERENCE
- Shah SJ, Feldman T, Ricciardi MJ, et al. One-year safety and clinical outcomes of a transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction in the Reduce elevated Left Atrial Pressure in patients with Heart Failure (REDUCE LAP-HF I) trial: A randomized clinical trial. JAMA Cardiol 2018;3:968-977.
Placement of an interatrial shunt device in patients with heart failure with preserved or mildly reduced ejection fraction did not lower the rate of heart failure events or improve health status.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content