The RELIEVE-HF trial evaluated the efficacy of interatrial shunting using the Ventura shunt in heart failure (HF) patients with reduced (HFrEF) and preserved ejection fraction (HFpEF). This global study randomised 508 participants to receive either the shunt or a placebo procedure, alongside optimal medical therapy. The study's primary endpoint—combining mortality, heart transplant or device implantation, HF hospitalisations, outpatient worsening, and quality of life changes—showed no significant difference between the shunt and placebo groups.
Notably, a prespecified subgroup analysis revealed that participants with HFrEF benefitted from the shunt, particularly in reduced HF hospitalisations, whereas HFpEF patients experienced increased death rates and hospitalisations, suggesting the intervention's benefits and risks are contingent on the type of heart failure. These findings highlight the importance of patient selection based on ejection fraction status in clinical decisions regarding interatrial shunting.
RELIEVE-HF highlighted notable differences in outcomes between HFrEF and HFpEF. What does this imply about the underlying pathophysiological distinctions?
"The primary takeaway from RELIEVE-HF is that the Ventura interatrial shunt is very safe for a severely ill HF population, though it didn't demonstrate overall efficacy. However, we observed a significant contrast in treatment effects between patients with reduced and preserved EF. Those with a baseline EF ≤40% saw substantial benefits, including a near 50% reduction in CV events and notably in HF hospitalisations. Conversely, for those with an EF ≥40%, the outcomes were detrimental, showing increased hospitalisations and a tripling in mortality. This suggests a potential role for interatrial shunts in patients with reduced EF, while their use in patients with preserved EF should be extremely cautious, if considered at all.
We have baseline and 1-year transthoracic echocardiographic data. Both HFrEF and HFpEF patients show increased left atrial volume and similar median pressures around 16 mmHg. However, their cardiac structures differ significantly; HFrEF patients have a dilated and weak left ventricle, accommodating the increased flow from the shunt. In HFpEF, the ventricles are normal-sized but stiff, leading to complications when accommodating additional fluid. This results in increased tricuspid regurgitation, pulmonary artery pressure, and potentially detrimental shifts in cardiac output."
Given these findings, would you recommend modifications to selection criteria for future studies or the clinical use of interatrial shunts in HF?
"Considering the baseline event rates in our study, there remains a substantial clinical need in HFrEF patients who had a significantly higher annual event rate compared with HFpEF patients. Future studies like ALLAY-HF (NCT05685303) and RESPONDER-HF (NCT05425459) are targeting a different, lower-risk HFpEF population. From what we've learned, HFrEF patients benefit markedly from shunt interventions, suggesting this group should remain a primary focus in future trials.
In the original REDUCE LAP-HF II trial (NCT03088033), it was surprising to see almost no mortality among the participants, given that they were an HF population [2]. The participants were considered low risk; eligibility required only exercise-induced increased pulmonary capillary wedge pressure. Although the overall results of the trial were negative, there appeared to be a subgroup within this very low-risk cohort that was at an even lower risk, showing lower natriuretic peptide levels and better cardiac function without right heart involvement. I believe there is a sweet spot for a small subset of patients with HFpEF, where shunts may not reduce their already low mortality risk, and these patients are also unlikely to require hospitalisation for HF. However, the real sweet spot identified in this trial was among patients with HFrEF. Despite only 206 participants randomised for shunt placement, a significant benefit was observed, marked by a P-value of less than 0.0001."
Do you support further testing of interatrial shunts in HFpEF patients?
"The findings from RELIEVE-HF open significant possibilities for HFrEF patients who have a great clinical need. We anticipate more clinical trials exploring various interatrial shunt designs tailored to this group. While HFpEF patients showed adverse effects, this insight is crucial for refining future interventions and could potentially redefine treatment approaches in HF management. I expect to see a lot more clinical trial activity, and we're going to learn a lot more in the next 5 years."
- Stone GW. A double-blind, randomized, placebo-procedure-controlled trial of an interatrial shunt in patients with HFrEF and HFpEF: principal results from the RELIEVE-HF trial. ACC 2024 Scientific Session, 6–8 April, Atlanta, USA.
- Shah SJ, Lancet. 2022;399(10330):1130-1140.
Copyright ©2024 Medicom Medical Publishers
Posted on
Previous Article
« Meet the Trialist: The EMPACT-MI trial findings Next Article
IMPROVE-HCM: Promising results for ninerafaxstat in non-obstructive HCM »
« Meet the Trialist: The EMPACT-MI trial findings Next Article
IMPROVE-HCM: Promising results for ninerafaxstat in non-obstructive HCM »
Table of Contents: ACC 2024
Featured articles
Matters of the heart: late-breaking news from the American College of Cardiology
Heart Failure and Cardiomyopathy
STEP-HFpEF DM: Semaglutide beneficial in patients with HFpEF and diabetes
IMPROVE-HCM: Promising results for ninerafaxstat in non-obstructive HCM
Acute Coronary Syndrome and Acute Myocardial Infarction
ACS: Necessary DAPT after PCI may be shorter than currently advised
AEGIS-II: ApoA-1 did not reduce MACE in patients with myocardial infarction but may provide benefit in patients with high LDL levels
REDUCE-AMI: Re-evaluating the role of routine beta-blockade in patients with acute myocardial infarction
Interventional Cardiology in 2024
Self-expanding versus balloon-expendable TAVR in patients with small aortic annuli
Safety of TAVI non-inferior to SAVR for patients with lower surgical risk
Interatrial shunt for HF: neutral primary endpoint but potential benefit in HFrEF
Peripheral artery disease: procedure-guidance by IVUS superior to angiography
IVUS-guided PCI beats angiography in patients with acute coronary syndrome
Addressing frailty in patients undergoing TAVR
Novel Developments in Risk Factor Management
Preventive PCI of vulnerable intracoronary plaque leads to favourable outcomes
KARDIA-2: Add-on zilebesiran effectively lowers blood pressure
BRIDGE-TIMI 73a: Olezarsen halves triglyceride levels
Plozasiran: A novel approach to severe hypertriglyceridaemia
High-risk and very high-risk patients meet LDL-cholesterol targets with lerodalcibep
No cardioprotective effect of ACE inhibitors in patients with cancer
Best of Posters
SGLT2 inhibition in heart failure more advantageous for women than men
Anxiety and depression: Lifestyle influential in MACE prevention
Meet the Trialists
Related Articles
© 2024 Medicom Medical Publishers. All rights reserved. Terms and Conditions | Privacy Policy
HEAD OFFICE
Laarderhoogtweg 25
1101 EB Amsterdam
The Netherlands
T: +31 85 4012 560
E: publishers@medicom-publishers.com