FDA approves first transseptal transcatheter mitral valve replacement system

Edwards Lifesciences said the U.S. Food and Drug Administration has approved its SAPIEN M3 mitral valve replacement system, making it the first transcatheter therapy using a transseptal approach cleared in the United States for the treatment of mitral regurgitation.

The system is approved for patients with symptomatic moderate-to-severe or severe mitral regurgitation who are considered unsuitable for surgery or transcatheter edge-to-edge repair by a multidisciplinary heart team. It is also approved for patients with symptomatic mitral valve dysfunction associated with mitral annular calcification, including moderate-to-severe or severe mitral regurgitation, severe mitral stenosis, or combined moderate mitral regurgitation and moderate mitral stenosis, when surgery or edge-to-edge repair are not options.

“Mitral regurgitation is very common among valvular heart diseases, and these patients often present with debilitating symptoms that are life-threatening and significantly diminish their quality-of-life. Up to this point, many patients were unsuitable for available treatment options, leaving the vast majority untreated and suffering,” said David Daniels, a cardiologist with Sutter West Bay Medical Group and structural heart section chief of Sutter’s Heart & Vascular Service Line. “The SAPIEN M3 system’s ability to provide a fully percutaneous mitral valve replacement that safely delivers near elimination of significant mitral regurgitation and meaningfully improves their symptoms is a game-changer for these patients.”

The transcatheter mitral valve replacement procedure involves two steps — delivery of a docking system followed by valve delivery — resulting in complete replacement of the native mitral valve. Both components are delivered through a percutaneous, 29F outer-diameter steerable guide sheath inserted through the femoral vein.

One-year results from the ENCIRCLE single-arm pivotal trial were presented Oct. 27, 2025, at the Transcatheter Cardiovascular Therapeutics conference and simultaneously published in The Lancet. In the main trial cohort of 299 patients deemed unsuitable for other treatment options, the study met all primary and secondary safety and effectiveness endpoints. Investigators reported significant elimination of mitral regurgitation, with 95.7% of patients achieving MR graded as 0 or 1+, along with meaningful improvements in symptoms and quality of life.

“Over our more than 65-year history, Edwards has continued to push the boundaries of structural heart innovation, and today, with the addition of mitral replacement to our portfolio of FDA-approved transcatheter therapies that already includes mitral repair, we are expanding the treatable patient population in the US,” said Daveen Chopra, corporate vice president for transcatheter mitral and tricuspid therapies at Edwards. “Edwards is once again transforming care for patients with the SAPIEN M3 system, which is built on the foundation of the proven SAPIEN platform and is supported by positive one-year ENCIRCLE pivotal trial data.”

The system received CE Mark certification in April 2025, making it the first approved transfemoral transcatheter mitral valve replacement system worldwide.

Advances reshape treatment of mitral valve disease

The approval comes amid rapid advances in the treatment of mitral valve disease, a condition that affects millions of patients worldwide and is especially prevalent among older adults and those with heart failure. For decades, open-heart surgery was the primary definitive treatment for severe mitral valve disease, leaving many patients untreated because of advanced age, frailty or multiple chronic conditions.

In recent years, minimally invasive catheter-based therapies have reshaped care by allowing physicians to repair or replace diseased valves through blood vessels rather than open surgery. Early efforts focused largely on repairing the mitral valve by clipping or approximating valve leaflets to reduce regurgitation. These approaches expanded access to treatment but were not suitable for all patients, particularly those with complex valve anatomy, extensive calcification or combined valve narrowing and leakage.

Technological progress has increasingly shifted toward full valve replacement delivered through catheters. Newer systems emphasize transseptal access — crossing from the right atrium into the left atrium — which avoids the need to puncture the chest wall or access the heart apex. This approach can reduce procedural risk, shorten recovery times and broaden the pool of patients who can be treated.

Imaging advances have also played a critical role. High-resolution echocardiography and cardiac CT scanning allow physicians to precisely assess valve anatomy, size replacement devices accurately and plan procedures tailored to individual patients. Improvements in delivery systems, including steerable catheters and lower-profile sheaths, have further enhanced safety and procedural success.

Clinical trials over the past several years have consistently shown that transcatheter mitral therapies can substantially reduce regurgitation, improve functional status and enhance quality of life in patients who previously had few or no viable treatment options. As evidence grows and devices continue to evolve, experts expect transcatheter mitral valve replacement and repair to become an increasingly important part of routine care for complex valve disease, particularly for patients who are not candidates for surgery.