Balloon-Expandable TAVI Superior to SAVR in Women at 1 Year: RHEIA

Female patients with symptomatic, severe aortic stenosis who undergo TAVI with a balloon-expandable Sapien 3 or Sapien 3 Ultra valve (Edwards Lifesciences) see better 1-year outcomes than those treated with surgical aortic valve replacement, the RHEIA trial suggests.

The difference was mainly due to a reduction in rehospitalization, researchers reported last weekend at the European Society of Cardiology Congress 2024.

RHEIA stands out as the first RCT comparing TAVI and SAVR exclusively in female patients, according to Hélène Eltchaninoff, MD (University Hospital of Rouen, France), who presented the findings in a Hot Line session. “In fact, there was a need for a randomized trial dedicated to women,” she told TCTMD, noting their tendency to have not only smaller annuli but also more fibrotic valves compared with men.

Earlier trials have shown that women fare better than men with TAVI, but the opposite is true with SAVR, Eltchaninoff added.

However, in her presentation, Eltchaninoff specified that the RHEIA findings “apply to a third-generation balloon-expandable valve system and cannot be extrapolated to other valve types.”

Indeed, “it’s difficult to say” how results might differ among valves, she acknowledged to TCTMD. But in terms of study design, “I think it’s good to have a homogeneous arm with one type of valve,” said Eltchaninoff.

There’s ongoing debate about which transcatheter heart valve is best for female patients over the long term. Earlier this year, a subgroup analysis of the SMART trial—87% of whose participants were female—showed that women with small aortic annuli seem to have better hemodynamic outcomes at 1 year after TAVI when treated with a self-expanding Evolut PRO/PRO+/FX valve (Medtronic) as opposed to Sapien 3/3 Ultra. Reassuring data from the PARTNER trials, meanwhile, indicate that early hemodynamics with the balloon-expandable valves do not adversely affect outcomes at 5 years in patients with small annuli.

Advantage Lies in Rehospitalization

For the investigator-initiated trial, which took place in 12 European countries between November 2019 and March 2023, researchers randomized 443 women (mean age 73 years; mean STS score 2.1-2.2%) with symptomatic, severe aortic stenosis to receive transfemoral TAVI with a Sapien 3 or Sapien 3 Ultra valve or SAVR. Among them, 215 TAVI patients and 205 SAVR patients had their procedure initiated, with 1-year follow-up available for approximately 97%.

Baseline patient characteristics were similar in the two groups apart from the TAVI patients having a lower prevalence of peripheral artery disease (2.3% vs 5.4%) and carotid artery stenosis (1.9% vs 3.9%). Mean gradient was 47 mm Hg, and mean ejection fraction was in the ballpark of 68%. Most of the patients—70.4% of the TAVI group and 75.5% of the SAVR group—had an annular area below 430 mm².

To start, TAVI patients had shorter hospital stays than SAVR patients (median 4 vs 9 days) and were more likely to be discharged home (90.2% vs 49.8%).

The primary endpoint, a composite of all-cause mortality, stroke, or rehospitalization for valve- or procedure-related symptoms or worsening of heart failure at 1 year, was 8.9% with TAVI and 15.6% with SAVR (HR 0.55; 95% CI 0.34-0.88). The difference met criteria not only for noninferiority but also superiority, with a P value of 0.03, and it was driven by rehospitalizations (4.8% with TAVI and 11.4% with SAVR; P = 0.02). All-cause mortality and stroke rates were similar in the two groups.

Additionally, the TAVI patients had less new-onset atrial fibrillation compared with the SAVR patients (3.3% vs 28.8%; P < 0.001) but were more likely to need permanent pacemaker implantation (8.8% vs 2.9%; P = 0.01) and had a higher prevalence of mild paravalvular aortic regurgitation at 1 year (15.5% vs 2.4%; P < 0.001). The rate of major vascular complications did not differ by treatment arm.

For echocardiographic outcomes, the mean gradient was similar in the TAVI and SAVR groups at baseline (47.8 vs 47.5 mm Hg; P = NS), but higher with TAVI than with SAVR at 30 days (13.6 vs 10.9 mm Hg) and 1 year (14.3 and 11.7 mm Hg; P < 0.001 for both). Effective orifice area for the TAVI and SAVR groups was 0.82 and 0.84 cm², respectively, at baseline (P = NS), though TAVI had significantly lower values at 30 days (1.81 vs 1.95 cm²; P = 0.007) and 1 year (1.74 vs 1.88 cm²; P = 0.01).

Still, these “excellent hemodynamics were achieved with both procedures in a population where around 75% of women had a small annulus,” Eltchaninoff pointed out. She noted that beyond TAVI’s positive impact on clinical outcomes, the less-invasive option also provides benefits in terms of reduced healthcare resources.

Anna Sonia Petronio, MD (Pisa University Hospital, Italy), the discussant following Eltchaninoff’s presentation, summed up the many pros and cons of both TAVI and SAVR in female patients. On the whole, “good preprocedural planning, proper valve selection, tailored implantation, and long-term management are essential for procedural success and minimizing complications, especially in low-risk younger women with a long life expectancy,” she concluded.

Early rehospitalization can be driven by a lot of factors, including physician bias in an unblinded trial. Joanna Chikwe

Commenting on the findings for TCTMD, cardiothoracic surgeon Joanna Chikwe, MD (Cedars-Sinai Medical Center, Los Angeles, CA), agreed that women are underrepresented in randomized trials of TAVI versus SAVR. “So it is possible that the results of these important trials may not apply equally to women, who are more likely to present with a small annulus, receive a small prosthesis, and experience higher mortality and complication rates after surgery compared to men,” she noted in an email.

However, she predicted that the main benefit seen here—a decrease in repeat hospitalization—wouldn’t differ much between TAVI devices.

Chikwe pointed out, also, that 13% of patients in the surgical arm underwent additional surgeries, such as ascending aorta replacement, other valve surgeries, and CABG. “This is important because the treatment benefit of surgery, particularly [with] complex procedures, typically only emerges in late follow-up” after approximately 3 to 5 years, she said. “Early rehospitalization can be driven by a lot of factors, including physician bias in an unblinded trial, and it remains very possible that surgery offers better long-term event-free survival than TAVR.”

Future research should address these limitations of RHEIA, she suggested.