Transfemoral TMVR a Limited Success in Early Feasibility Study

It remains early days for transcatheter mitral-valve replacement (TMVR) as a minimally invasive way to treat severe, mitral regurgitation (MR), but it’s even earlier days for TMVR as an endovascular procedure. Most of the technique’s limited experience with a dedicated mitral prosthesis has involved transapical delivery.

But now a 15-patient study of transfemoral, transeptal TMVR — with a prosthesis designed for the mitral position and previously tested only transapically — has shown good 30-day results in that MR was essentially abolished with virtually no paravalvular leakage.

Nor were there adverse clinical events such as death, stroke, reintervention, or new need for a pacemaker in any of the high-surgical-risk patients with MR in this feasibility study of the transfemoral Intrepid TMVR System (Medtronic). Implantation failed, however, in one patient who then received a surgical valve via sternotomy.

The current cohort is part of a larger ongoing trial that will track whether patients implanted transfemorally with the Intrepid also show reverse remodeling and good clinical outcomes over at least a year. That study, called APOLLO, is one of several exploring dedicated TMVR valves from different companies, with names like SUMMIT, MISCEND, and TIARA-2.

Currently, TMVR is approved in the United States only using one device designed for the aortic position and only for treating failed surgical mitral bioprostheses in high-risk patients.

If the Intrepid transfemoral system has an Achilles’ heel, at least in the current iteration, it might be its 35 F catheter delivery system that requires surgical access to the femoral vein. Seven of the patients in the small series experienced major bleeding events, including six at the femoral access site, listed as major vascular complications.

Overall, the study’s patients “were extremely sick with a lot of comorbidity. A lot of them had atrial fibrillation, a lot of them were on anticoagulation to start with,” observed Firas Zahr, MD, Oregon Health & Science University, Portland, Oregon, as part of his presentation of the study at Transcatheter Cardiovascular Therapeutics (TCT) 2021, held virtually as well as onsite in Orlando, Florida.

All had moderate-to-severe, usually primary MR; two thirds of the cohort had been in NYHA class III or IV at baseline, and 40% had been hospitalized for heart failure within the past year. Eight had a history of cardiovascular surgery, and eight had diabetes. Their mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS-PROM) score was 4.7, Zahr reported.

“At 30 days, there was a significant improvement in their heart failure classification; the vast majority of the patients were [NYHA] class I and class II,” said Zahr, who is also lead author on the study’s November 6 publication in JACC: Cardiovascular Interventions.

Observers of the study at TCT 2021 seemed enthusiastic about the study’s results but recognized that TMVR in its current form still has formidable limitations.

“This is clearly an exciting look into the future and very reassuring to a degree, aside from the complications, which are somewhat expected as we go with 30-plus French devices,” Rajiv Tayal, MD, MPH, said at a press conference on the Intrepid study held before Zahr’s formal presentation. Tayal is an interventional cardiologist with Valley Health System, Ridgewood, New Jersey, and New York Medical College, Valhalla, New York.

“I think we’ve all learned that transapical [access] is just not a viable procedure for a lot of these patients, and so we’ve got to get to transfemoral,” Susheel K. Kodali, MD, interventional cardiologist at NewYork-Presbyterian/Columbia University Irving Medical Center, New York City, said at the same forum.

A 35 F device “is going to be too big,” he said. However, “it is the first step to iterate to a smaller device.” Kodali said his center contributed a patient to the study, and he is listed as a coauthor on the publication.

The delivery system’s large profile is only part of the vascular complication issue. Not only did the procedure require surgical cutdown for venous access, “we were fairly aggressive in anticoagulating these patients with the fear of thrombus formation,” Zahr said in the discussion following his presentation.

“A postprocedure anticoagulation regimen is recommended within the protocol, but ultimate therapy was left to the discretion of the treating site physician,” the published report states, noting that all 14 patients with successful TMVR were discharged on warfarin. They included 12 who were also put on a single antiplatelet and one given dual antiplatelet therapy on top of the oral anticoagulant.

“One thing that we learned is that we probably should standardize our approach to perioperative anticoagulation,” Zahr observed. Also, a 29 F sheath for the system is in the works, “and we’re hoping that with smaller sheath size, and hopefully going even to percutaneous, might have an impact on lowering the vascular complications.”

Explanations for the “higher-than-expected vascular complication rate” remains somewhat unclear, agreed an editorial accompanying the study’s publication, “but may include a learning curve with the system, the large introducer sheath, the need for surgical cutdown, and postprocedural anticoagulation.”

For transseptal TMVR to become a default approach, “venous access will need to be achieved percutaneously and vascular complications need to be infrequent,” contends the editorial, with lead author Mohamad Alkhouli, MD, Mayo Clinic, Rochester, Minnesota.

“These data provide a glimpse into the future of TMVR. The excellent short-term safety and effectiveness of this still very early-stage procedure represent a major step forward in the field,” they write.

“The main question that the Intrepid early feasibility data raise is whether transfemoral, transseptal TMVR will evolve to become the preferred strategy over transapical TMVR,” as occurred with transcatheter aortic-valve replacement (TAVR), the editorial states. “The answer is likely yes, but a few matters specific to transseptal route will need be addressed first.”

Among those matters: the 35 F catheter leaves behind a considerable atrial septal defect (ASD). At operator discretion in this series, 11 patients received an ASD closure device.

None of the remaining four patients “developed significant heart failure or right ventricular dysfunction,” Zahr observed. “So, it seems like those patients who had their ASD left open tolerated it fairly well, at least until 30 days.”

But “we still need to learn what to do with those ASDs,” he said. “What is an acceptable residual shunt and what is an acceptable ASD size is to be determined.”

In general, the editorial notes, “the TMVR population has a high prevalence of cardiomyopathy, and a large residual iatrogenic ASD may lead to worsening volume overload and heart failure decompensation in some patients.”

Insertion of a closure device has its own issues, it continues. “Closure of the ASD might impede future access to the left atrium, which could impact life-long management of this high-risk population. A large septal occluder may hinder potentially needed procedures such as paravalvular leak closure, left atrial appendage closure, or pulmonary vein isolation.”

Patients like those in the current series, Kodali observed, will face “a lifetime of management challenges, and you want to make sure you don’t take away other options.”

The study was funded by Medtronic. Zahr reported institutional grant support from Edwards Lifesciences and Medtronic. Kodali disclosed consultant fees from Admedus and Dura Biotech; equity in Dura Biotech, Microinterventional Devices, Thubrika Aortic Valve, Supira, Admedus, TriFlo, and Anona; and institutional grant support from Edwards Lifesciences, Medtronic, Abbott Vascular, Boston Scientific, and JenaValve. The editorial writers have disclosed no relevant financial relationships. Tayal disclosed consultant fees or honoraria from or serving on a speakers bureau for Abiomed, Edwards Lifesciences, Abbott Vascular, and Shockwave Medical.

Transcatheter Cardiovascular Therapeutics (TCT) 2021: Late-Breaking Clinical Science Session III. Presented November 6, 2021.

JACC Cardiovasc Interv. Published online November 6, 2021. Abstract, Editorial

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