The RELIEVE-HF study: is an atrial septal shunt beneficial in HFrEF?
Reported from ACC.24
Charles Fauvel provides his take on the RELIEVE-HF study outcomes presented by Gregg W. Stone at ACC.24 in Atlanta.
Key Messages
- Atrial septal shunt devices are currently being studied in heart failure (HF), as they allow for left atrial unloading, thus reducing pulmonary congestion.
- This study investigated the V-wave Ventura device and demonstrated the safety of this device.
- Although negative for the primary endpoint, the pre-specified analysis in HF patients with an LVEF ≤ 40 % showed potential interest in this population.
Introduction
Heart failure (HF) is characterized by an increase in left atrial pressure (LAP), leading to initial pulmonary venous congestion. LAP, which rises during exertion and hypervolemia, can be challenging to regulate pharmacologically.
Preliminary studies have already shown that atrial septal shunt devices can reduce LAP to improve HF symptoms and alter prognosis1-3.
Pilot studies have shown that the Ventura IAS system allows for a reduction in filling pressures and an improvement in cardiac function, while improving symptoms in patients with either preserved (HFpEF) or reduced (HFrEF) ejection fraction.
The objective of this study was to evaluate the safety and efficacy of the Ventura IAS system in symptomatic HF patients, regardless of LVEF.
Population and Design
The RELIEVE-HF study was a multicenter, double-blind, stratified (LVEF ≤ 40 % vs. LVEF > 40 %) randomized placebo-controlled study involving patients with:
- HF, of ischemic or non-ischemic origin, regardless of LVEF, documented for at least 6 months.
- NYHA class II-IV, despite maximal recommended HF treatment (including electrical treatment).
- Hospitalization for HF in the past 12 months and/or elevated natriuretic peptides (adjusted for BMI), both required for NYHA II.
- A 6-minute walk test distance between 100 m and 450 m.
Exclusion criteria included:
- Systolic BP < 90 or > 160 mmHg.
- Severe pulmonary hypertension defined by an echographic sPAP > 70 mmHg or pulmonary vascular resistance > 4 Wood units in right heart catheterization.
- Right ventricular dysfunction: TAPSE < 12 mm or fractional shortening ≤ 25% in echocardiography.
- Left ventricular dilation over 8 cm in echocardiography.
- Severe uncorrected valvulopathy, history of ASD, PFO, PAPVR, or operated congenital heart disease.
- Transseptal puncture for another indication within the past 6 months.
Endpoints
The primary endpoint was a hierarchical efficacy endpoint (win-ratio analysis) comprising:
- All-cause mortality.
- Heart transplantation or left ventricular assist device implantation.
- HF hospitalizations.
- Worsening of HF in outpatient settings.
- A minimum 5-point difference in the KCCQ score between baseline and one year.
The safety endpoint included: death, stroke, systemic embolism of the prosthesis, or the need for cardiac surgery within 30 days of the procedure.
All analyses were stratified by LVEF (> 40 % vs. ≤ 40 %).
Main Results
1,136 patients were screened across 113 sites, and 508 patients were finally randomized: 250 in the shunt group, and 258 in the placebo procedure group.
- The average age was 75 years, about half (45 %) had ischemic HF, 60 % had a history of atrial fibrillation, and ¼ were resynchronized.
- The majority of patients (96 %) were in NYHA class III, with an average 6-minute walk test distance of 265 m. The NTproBNP level was 1,939 pg/mL in the shunt group, and 1,596 pg/mL in the placebo group.
- 40 % of included patients had an LVEF ≤ 40 %.
Baseline echographic data showed a TAPSE around 17 mm, an echographic sPAP of 32 mmHg, moderate or greater MR in 20 % of cases in the shunt group (14.7 % in the placebo group), and moderate or greater TR in 20.2 % of cases in the shunt group (17.5 % in the placebo group).
Baseline hemodynamic data showed a right atrial pressure of 9.0 mmHg, a mean PAP of 25 mmHg, and pulmonary vascular resistance of 2.0 Wood units.
The average procedure time was 80 minutes in the shunt group, versus 43 minutes in the placebo group.
Regarding the safety endpoint, there were no procedure-related complications in the shunt group, which was below the predefined threshold of 11 % (p < 0.0001).
Regarding the primary endpoint, the win-ratio analysis did not show a benefit of the V-wave prosthesis versus the placebo procedure: 0.86, 95 % CI [0.61-1.22], p = 0.20.
Interestingly, the stratified analysis by LVEF showed a significant reduction in the primary endpoint in the LVEF ≤ 40 % group: HR = 0.55, 95 % CI [0.42-0.73], p < 0.0001.
Of course, these results are only applicable to the use of the V-wave shunt system. The subgroup analysis, stratified by LVEF, although pre-specified, should be considered exploratory, and further studies are necessary to confirm or refute these results.
Conclusion
The RELIEVE-HF study using the V-wave Ventura atrial septal shunt device did not show the benefit of the device in improving symptoms and prognosis in HF patients, regardless of LVEF.
However, a pre-specified analysis suggests potential interest in patients with LVEF ≤ 40%, and potentially deleterious effects in the opposite case.
References
- Griffin JM, Borlaug BA, Komtebedde J, Litwin SE, Shah SJ, Kaye DM, et al. Impact of Interatrial Shunts on Invasive Hemodynamics and Exercise Tolerance in Patients With Heart Failure. J Am Heart Assoc. 2020 Sep;9(17):e016760.
- Shah SJ, Feldman T, Ricciardi MJ, Kahwash R, Lilly S, Litwin S, 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 Oct 1;3(10):968–77.
- Obokata M, Reddy YNV, Shah SJ, Kaye DM, Gustafsson F, Hasenfuβ G, et al. Effects of Interatrial Shunt on Pulmonary Vascular Function in Heart Failure With Preserved Ejection Fraction. J Am Coll Cardiol. 2019 Nov 26;74(21):2539–50.
This review was originally published here https://www.cardio-online.fr/Actualites/A-la-une/ACC-2024/Etude-RELIEVE-HF-ACC-2024 and has been reused with permission from the author.
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