Safety and mortality results in the Intrepid trial at one-year

The study evaluated 33 patients enrolled in the early feasibility trial, focusing on safety and mortality outcomes. Zahr reported zero mortality at both 30 days and six months, which he said was a noteworthy achievement. At the one-year mark, the mortality rate stood at 6.7%, with only two patients succumbing between six to 12 months. These results are highly encouraging, he said, indicating the safety and viability of the transfemoral TMVR approach.

"That mortality rate is very encouraging for this therapy. There were zero strokes both at 30 days and at one year, and the complication rate was very favorable," Zahr said. 

The average procedure time for device insertion was approximately 45 minutes in the early feasibility trial.

Zahr emphasized the study focused on patients with moderate to severe mitral regurgitation, specifically those believed to face a high surgical risk by their heart team. These patients, often elderly and frail, represent a challenging demographic for traditional surgical interventions. The trial is designed to follow patients for up to five years, with the reported one-year outcomes demonstrating excellent valve hemodynamics and performance.

Bleeding complications and vascular access with a 35 French device  

While the study demonstrated overall favorable outcomes, Zahr acknowledged initial challenges related to vascular complications and bleeding events. These issues were predominantly observed in the first 15 patients and were attributed to the learning curve associated with the procedure. However, with ongoing improvements in procedural management and changes in anticoagulation strategies, the incidence of complications, including bleeding, significantly decreased.

The current iteration of the Intrepid device is large 35 French, but Zahr anticipates this to evolve into a smaller 29 French version in the near future. The current larger device required a surgical cut down to gain vascular access and leaves a sizable hole in to septum where it crosses to gain access to the mitral valve.

Zahr said operators in the trial have been using a combination of sutures or a closure device to close the assess site. 

For the hole in the septum, he said they have not closed most of atrial septal defects (ASD) unless they cause an issue. Not using closure devices ensures septal access can be used again in the future if a patient needs another valve intervention or left atrial appendage occlusion. Zahr said most septal punctures for the MitraClip are not closed for the same reason. 

"Leaving the septum not closed has significant advantages. And for those who did not have their septum closed, we did not see negative signals in terms of right ventricular dysfunction or increased severity of tricuspid regurgitation. Really all the signals are pushing us to say we're going to close less ASDs. And with the delivery system getting even smaller, we're going to feel more confident about that," Zahr explained.

LVOT considerations with the Intrepid valve

Zahr discussed the challenge of left ventricular outflow tract (LVOT) obstruction, acknowledging its complexity and dynamic nature. When a valve is placed in the small mitral annulus landing zone, any overhang into the left ventricle can block blood flow to the aortic valve. The study indicated that, despite initial concerns, the majority of patients did not experience significant LVOT obstruction at one year. But he said all the patients evaluated for this trial underwent a rigorous screening process and CT evaluation that included placing simulated valves in the anatomy to determine if LVOT blockage would be an issue. Patients were screened out of the trial if there was an expected issue with the valve and a patient's anatomy. 

One patient had a fixed LVOT obstruction that required the device to be surgically explanted three days post-procedure. Three patients had dynamic LVOT obstruction, which resolved in subsequent followups. 

"Obviously we still need to work on the high screen fail in terms of LVOT obstruction, but I'm really hoping that the next-generation device with the 29 French size and with larger valve sizes can translate into including more and more patients," Zahr said. 

Anchoring mechanism for the Intrepid valve

One complexity of developing a transcatheter mitral valve has been how to anchor it in position without complications from the attached cordi tendini, and an annulus that is usually D-shaped and often had a saddle curve. The device also cannot drop too far down into the ventricle because of LVOT obstruction. The Intrepid device employs anchors that stabilize the valve on the mitral annulus. 

"There are anchors that get into the tissue. They don't penetrate all the way through the muscles, but what they do is they anchors on the leaflets and the analysts and stabilize the valve in place. Also, the valve has a champagne cork shape, so there is a part that is underneath the mitral annulus that helps stabilize the valve by oversizing keeps it in place," Zahr said.  

He said there are multiple advances in the valve and the delivery system that turn what was thought to be a very complicated procedure and made it a lot simpler.