Heart failure outcomes after interatrial shunt implant vary by ejection fraction
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Key takeaways:
- Interatrial shunt implant lowered HF hospitalization risk for patients with HFrEF vs. placebo.
- However, patients with HFpEF had more than threefold increased risk for all-cause mortality.
ATLANTA — Transcatheter implant of an interatrial shunt had drastically different results depending on ejection fraction in patients with HF, a speaker reported at the American College of Cardiology Scientific Session.
The shunt reduced risk for HF hospitalization in patients with HF with reduced EF compared with placebo at 2 years, Gregg W. Stone, MD, professor of cardiology and population health sciences at Icahn School of Medicine at Mount Sinai and director of academic affairs for the Mount Sinai Health System, said during a presentation.
In contrast, shunt implant increased the risk for all-cause death by more than threefold and HF hospitalization by more than twofold in patients with HF with preserved EF compared with placebo, according to the results of the double-blind, randomized placebo-procedure-controlled RELIEVE-HF trial.
“Transcatheter implantation of the Ventura interatrial shunt was safe but did not reduce symptoms or improve prognosis through 2 years in patients with heart failure across the full range of left ventricular ejection fraction,” Stone said during the presentation. “However, the results from prespecified stratified analysis suggest that interatrial shunt implantation is beneficial in patients with reduced left ventricular ejection fraction and harmful in patients with preserved LVEF.”
For the RELIEVE-HF trial, Stone and colleagues evaluated whether the implant of an interatrial shunt (Ventura, V-Wave Ltd.) could improve left atrial pressure, HF symptoms and prognosis in a cohort of patients with HF at varying EF ranges. Reduced EF was defined as EF of 40% or less and preserved EF was defined as EF more than 40%.
The shunt is implanted via 14 French delivery system and creates a 5.1 mm orifice in the fossa ovalis. In the left atrium, expanded polytetrafluoroethylene channels blood flow into the right atrium while preventing lumen loss. In the right atrium, an “exit hood” blocks paradoxical emboli transit. Those who receive shunt implant then receive 6 months of dual antiplatelet therapy.
The primary effectiveness endpoint was a hierarchical composite of all-cause death, heart transplant or left ventricular assist device implant, HF hospitalization, all outpatient worsening HF events and a 5-point minimum change in Kansas City Cardiomyopathy Questionnaire (KCCQ) score from baseline to 12 months.
The primary safety endpoint was device-related or procedure-related adverse CV events including all-cause death, stroke, systemic embolism, need for open cardiac surgery or need for major endovascular surgical repair at 30 days. The Outpatient Procedure Component goal was less than 11%.
A total 508 patients at 113 sites in 11 countries were randomly assigned and matched 1:1 to either interatrial shunt (mean age, 74 years; 65% men) or sham procedure (mean age, 72 years; 61% men).
The shunts were implanted successfully in all participants, with an average procedure time of 80 minutes and an average fluoroscopy time of 14 minutes. The post-procedure hospital stay was 1 day in both the shunt and placebo arms.
Over a median follow-up of 22 months, the primary effectiveness endpoint did not differ between the groups in the overall cohort (phase-weighted win ratio, 0.86; 95% CI, 0.61-1.22; P = .2), Stone said during the presentation, noting the annualized rate of events also did not differ between the groups (relative rate ratio = 1; 95% CI, 0.83-1.2; P = .96), nor did the rates of the individual components of the primary effectiveness endpoint.
KCCQ score improved from baseline in both groups but did not differ between the groups in the overall cohort (P = .74), Stone said.
No device-related or procedure-related adverse CV events had occurred by 30 days or 2 years.
In patients with HFpEF, those assigned shunting had significantly increased risk for all-cause death (RR = 3.24; 95% CI, 1.38-7.59), HF hospitalization (RR = 2.05; 95% CI, 1.35-3.1) and the total rate of all-cause death, heart transplant, LVAD, all HF hospitalizations and all outpatient worsening HF events (annualized HR = 1.68; 95% CI, 1.29-2.19) at 2 years, Stone said.
In significant contrast (P for interaction for all < .05), compared with placebo, interatrial shunting in patients with HFrEF reduced the risk for HF hospitalizations (RR = 0.52; 95% CI, 0.31-0.86) and the total rate of all-cause deaths, heart transplants, LVADs, HF hospitalizations and outpatient worsening HF events (annualized HR = 0.55; 95% CI, 0.42-0.73) and showed a trend toward reduced risk for all-cause death (RR = 0.63; 95% CI, 0.31-1.26).
The interatrial shunt received a CE mark and is approved to be marketed for use in the European Union, but is not yet approved for commercial use in the United States.
“The present results apply only the profile of patients enrolled and treated with this particular interatrial shunt. Reduced and preserved ejection fraction groups, a prespecified randomized strata, were not individually powered for effectiveness. The results within each strata must therefore be considered exploratory,” Stone said during the presentation. “However, the strong interaction and the spline curve analysis for cardiovascular events essentially showing a dose-response curve suggests that these findings are not due to a play of chance. The large similar increase in KCCQ in both the device and control groups emphasize the relevance of the placebo effect and the necessity for blinded trials.”
Reference:
- Impact of Interatrial Shunt May Vary by Heart Failure Type. https://www.acc.org/About-ACC/Press-Releases/2024/04/06/12/33/impact-of-interatrial-shunt-may-vary-by-heart-failure-type. Published April 6, 2024. Accessed April 6, 2024.
- V-Wave Receives CE Mark for the Ventura Interatrial Shunt System. https://vwavemedical.com/v-wave-receives-ce-mark-for-the-ventura-interatrial-shunt-system/. Published March 5, 2020. Accessed April 6, 2024.
Perspective
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Strictly speaking, it was a negative trial. We need to take all of the subgroup analysis with a grain of salt. But the surprising thing about that trial is the disparity between what’s going on with ejection fractions under 40% and above 40%. What’s most surprising about that is that we typically think of interatrial shunts for highly selected patients who have HFpEF with EFs above 40%. It was interesting to see that it was negative or even harmful in that group. But again, it’s difficult to draw that conclusion based on the subgroup.
The problem with the HFpEF population is that they are a cardiometabolic sick population. They have a lot of comorbidities. They have diabetes, histories of stroke, coronary artery disease, cerebral vascular disease and they tend to be also obese, less mobile and older. So those patients are prone to having strokes. They’re also prone to having acute coronary syndromes, MIs and things like that.
It’s too early to say whether the shunt is the cause of that, especially looking at the numbers that we have in the subgroup. But it is also important to understand that that patient population typically is older, sicker, more comorbid and more prone to those events in general with or without a device intervention.
You need to get a little bit more nuanced with the understanding of pulmonary hypertension. The exclusions for pulmonary hypertension were in the study, but in general, we need to understand more about the interaction between pulmonary hypertension and right ventricular function in those patients with HFpEF. The danger in doing an interatrial shunt in those groups is that that shunt can reverse and that would definitely put you at higher risk for things like stroke and potentially acute MIs. A more nuanced understanding of that would make a lot of sense for future trials.
Historically, the interatrial shunt was used for patients with mitral stenosis. That’s when it was first physiologically made plausible and used for palliation in end-stage heart failure due to mitral stenosis. Reduction of the pulmonary capillary wedge pressure with a shunt may be beneficial for those patients. We also know that in patients with HFrEF, chronically elevated left-sided filling pressures are more associated with mortality than even cardiac output, cardiac index in those measures. So it is possible, or at least plausible that if you can reduce or unload the left atrium, then maybe that would confer some benefit. But again, it’s too early to tell and it’s difficult to draw that kind of conclusion from this study.
We need to understand a little bit more about the subgroups; who those patient populations are; what exactly the mortality was. When it comes down to a device like this, it’s all about patient selection. So we just need to figure out who is the patient who may benefit the most.
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Stone GW, et al. Late-breaking clinical trials I. Presented at: American College of Cardiology Scientific Session; April 6-8, 2024; Atlanta.
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