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In August 2019, the U.S. Food and Drug Administration (FDA) approved transcatheter aortic valve replacement (TAVR) for patients with severe aortic stenosis who are at low risk of death or complications from open heart surgery. Researchers at �ٺ���Ƶ Health played a pivotal role in that decision and are developing new techniques to further advance TAVR clinical practice.

Continued Leadership in Transcatheter Aortic Valve Replacement

The FDA ruling was based on two multisite clinical studies: the PARTNER 3 trial, which gauged the safety and effectiveness of the Edwards SAPIEN 3 device in low-risk patients; and the Evolut Low Risk Trial, which tested the CoreValve™, Evolut™ R, and Evolut™ PRO valves.

�ٺ���Ƶ’s Heart Valve Center was the nation’s third-largest enroller in PARTNER 3, in which 497 patients were randomized to surgical aortic valve replacement (SAVR) and 503 to TAVR. The nonsurgical procedure proved superior to SAVR at preventing death, stroke, or rehospitalization within two years. TAVR also was associated with a shorter hospital stay, a lower incidence of atrial fibrillation, and a larger improvement in quality of life.

The Evolut trial reached similar conclusions.

“These studies showed that the advantages of TAVR apply to patients at all risk levels and that almost everyone with this disease can be treated without open heart surgery,” says Mathew R. Williams, MD, chief of �ٺ���Ƶ’s and director of the Heart Valve Center.

A Trailblazing Team

Under the direction of Dr. Williams, a widely recognized pioneer in transcatheter valve replacement techniques, the Heart Valve Center has become a national training site for TAVR best practices, with doctors implanting more than 450 of the devices in 2019. The center also has the busiest transcatheter mitral valve replacement (TMVR) practice on the East Coast and offers a full array of open, minimally invasive, and robotic procedures.

Dr. Williams, associate professor in the Departments of and , has performed more than 3,500 such procedures, more than any other surgeon in the country. His record includes two first-in-human and three first-in-U.S. implants.

Dr. Williams also was the lead primary investigator in the Evolut™ R and Evolut™ PRO premarketing studies, which led to those devices’ approval for high-risk patients in 2015 and 2017.

“Our outcomes are among the best in the country, thanks to a specialized team of surgeons, anesthesiologists, radiologists, and nurses who have performed these procedures together thousands of times,” notes Dr. Williams, who was the first surgeon in the United States to be dual-trained in interventional cardiology and cardiac surgery.

�ٺ���Ƶ’s TAVR patients have a 99 percent survival rate, and a significantly lower rate of stroke, bleeding, and other complications than the U.S. average. More than 99 percent of procedures are performed without general anesthesia. Most patients leave after an overnight stay, compared with a national median of two days.

Advancing a Precision Medicine Approach to TAVR

The Heart Valve Center is committed to advancing patient-specific surgical techniques that can lower the risk of complications and improve outcomes. A found that a new approach to device implantation could minimize the risk of permanent pacemaker implantation (PPMI) in patients receiving repositionable self-expanding TAVR. The study was led by Dr. Williams and Hasan Jilaihawi, MD, associate professor of cardiothoracic surgery and medicine and co-director of transcatheter valve therapy.

One drawback to TAVR compared with SAVR is an elevated risk of PPMI. This risk has historically been higher with self-expanding TAVR than with balloon-expanding TAVR. Device positioning has emerged as an important determinant in PPMI, with higher TAVR implantation resulting in lower rates of pacemaker implantation. Recent iterations of self-expanding TAVR devices are repositionable, which provides a further opportunity to reduce the risk of PPMI by intraprocedural optimizing of device positioning. Yet, no formula has existed for determining optimal positioning for any given patient.

The MIDAS Touch

The �ٺ���Ƶ team retrospectively studied 248 patients who had undergone a standard approach to self-expanding repositionable TAVR implantation. A detailed analysis of anatomic, electrophysiological, and procedural factors contributing to PPMI in this context suggested that a key variable was depth of positioning relative to the length of a patient’s membranous septum. PPMI rates were uniformly high if implant depth was more than membranous septum length, and uniformly low if implant depth was less than membranous septum length.

Using this information, the researchers performed a prospective study based on an approach labeled MIDAS (minimizing depth according to the membranous septum). Operators attempted to position the prosthesis at a pre-release depth that was smaller than the length of the membranous septum, as measured from the noncoronary cusp.

Researchers followed 100 consecutive patients after discharge for at least 30 days. The results were striking: The new PPMI rate in the MIDAS group was 3.0 percent, versus 9.7 percent in the standard group.

“With the expansion of TAVR to low surgical risk patients,” Dr. Williams observes, “it’s reassuring that rates of PPMI equivalent to or potentially even lower than surgery may be achieved through this precision medicine–based approach.”

Ongoing Innovation at the Heart Valve Center

In the coming year, the Heart Valve Center will continue to investigate novel treatments for heart valve disease, including new TAVR devices that can be fully deployed and then recaptured, a new percutaneous mitral valve repair device, and the next-generation mitral valve clip. Additionally, the center was recently chosen as a study site for the APOLLO trial of Medtronic’s Intrepid TMVR device, which is implanted through a transapical approach on a beating heart.

In addition, the Heart Valve Center will soon begin enrolling patients in a pivotal trial of Abbott’s TriClip device—the first transcatheter treatment for severe tricuspid valve disease. Tricuspid valve regurgitation can lead to heart failure that is often resistant to medical therapy. Many patients are at high risk for conventional surgery and thus lack effective treatment options. In the multicenter TRILUMINATE Pivotal trial, approximately 700 patients will be randomized to medical therapy versus the TriClip device. (The study also will have a nonrandomized arm for treatment of subjects with more complex disease.) Results from an earlier phase of the study, presented at EuroPCR in May 2019, found that after 30 days, 86.6 percent of patients who received the TriClip saw reduced tricuspid valve regurgitation severity of at least one grade.

Disclosure: Mathew R. Williams, MD, receives research funding from Edwards Lifesciences and Medtronic.