Beyond MitraClip! Transcatheter Mitral Valve Replacement Clears First-in-Human Hurdle

October 20, 2014

VANCOUVER, BC — A Canadian group has successfully implanted a bioprosthetic pericardial valve (Tiara, Neovasc) with a minimally invasive transapical-access strategy in two patients with severe functional mitral regurgitation (MR)[1].

The transcatheter mitral-valve replacement (TMVR), in which the device is inserted through the left ventricular apex that has been exposed with a 4-cm anterior minithoracotomy, was performed by Dr Anson Cheung (St Paul's Hospital, Vancouver, BC) and colleagues in a 73-year-old man and 61-year-old woman who were deemed too high risk for mitral-valve replacement surgery. The implantation took place in a hybrid operating room with a multidisciplinary team, including an interventional cardiologist and cardiac surgeon, and was deemed safe and feasible.

As reported October 20 in the Journal of the American College of Cardiology, a postimplantation left-ventricular angiogram showed there was no significant MR and measurements confirmed an unobstructed left-ventricular outflow tract. A transesophageal echocardiogram (TEE) revealed the valve was securely anchored and normal valve function was achieved. Regarding paravalvular leakage, the investigators say it was "trivial." Both patients were hemodynamically stable throughout the procedure.

The 61-year-old woman, who had heart failure with NYHA class 3 or 4 symptoms, was initially referred for transplantation. She had multiple comorbidities, including hypertension, obstructive lung disease, atrial fibrillation, and liver cirrhosis. Her baseline STS risk score was 4.5%. Five days after TMVR, she was discharged from the hospital.

The man, also deemed too high risk for surgery, had an STS risk score for mitral-valve replacement of 47.7%. He had severe left ventricular dysfunction and an ejection fraction that ranged from 15% to 20%. He died of end-stage heart failure at day 69 despite a "well-functioning prosthesis and elimination of MR," say investigators.

Lots of Unanswered Questions

Like transcatheter aortic-valve replacement (TAVR), which has changed the management of patients with aortic stenosis, a catheter-based approach for MR "may present another chapter in the evolution in the treatment of valvular heart disease," according to the researchers. However, as an editorial points out, for that to happen,  many unanswered questions must be resolved[2].

Drs Anelechi Anyanwu and David Adams (Icahn School of Medicine, Mount Sinai, New York, NY) write that the investigational prosthetic valve has a complex design, including anchoring mechanisms that prevent the valve from moving during ventricular contraction, because the mitral valve has an "intricate pathoanatomy and lack of a rigid landing zone."

Most importantly, the editorialists point out that although TAVR has enjoyed rapid and explosive clinical adoption and growth, TMVR differs substantially from the percutaneous replacement of the aortic valve. First, the vast majority of aortic-valve interventions are for degenerative calcific aortic stenosis, but mitral-valve disease has more than one cause. Mitral regurgitation and mitral stenosis can have a congenital, degenerative, rheumatic, or postendocarditis etiology, or they might be secondary to ventricular or atrial pathologies. A single transcatheter prosthetic solution for such a heterogenous disease is more challenging than one for aortic-valve disease, say the editorialists.

Secondly, mitral-valve disease is not confined to the elderly, and this raises concerns about the durability of the prosthetic valve and long-term outcomes. "Applying a less invasive, untested technology would be more controversial in young mitral-regurgitation patients who may have several decades of life expectancy than in elderly aortic stenosis patients with an average life expectancy less than 10 years," write Anyanwu and Adams.

Other Concerns

Regarding some of the other key differences between TAVR and TMVR, the editorialists note:

  • Aortic-valve replacement is the default strategy for aortic-valve stenosis, but this isn't the case for mitral-valve disease; mitral-valve repair is the recommended intervention for severe MR.

  • With TAVR, paravalvular leaks are well-tolerated and -managed, but the consequences of a mitral-valve leak with TMVR are not certain; data suggest that mitral paravalvular leaks carry a greater burden of morbidity and mortality than aortic leaks, say the editorialists.

  • Mitral-valve disease is not associated with a high risk of death in the short term, unlike aortic-valve disease. Although mitral-valve disease reduces life expectancy, the effect occurs over years rather than months. "The urgency and short-term benefits of mitral-valve intervention (over medical therapy) are therefore minimal and swing the bias away from using percutaneous device therapy as a life-extending intervention," write Anyanwu and Adams.

Also at play is the question of "inoperability." Given the success of surgery, TMVR will likely initially be restricted to patients who are not candidates for surgery. However, as the editorialists write, the definition of inoperability is flexible. Anyanwu and Adams say that many surgeons would argue that the woman treated—given her STS risk score of 4.5%—could have undergone mitral-valve surgery.

At present, the American College of Cardiology/American Heart Association say that mitral-valve surgery is a class IIb indication for patients with functional MR, meaning that practitioners are divided on the basis for surgery in such a patient. "If the benefit of surgery is unclear and unproven in such patients, is experimental percutaneous mitral replacement justified?" ask the editorialists.

On the whole, the editorialists say that Cheung and colleagues should be congratulated for their pioneering effort, an effort that "makes it probable TMVR will be technically possible in the near future." Before TMVR takes off like TAVR, however, the key issues they raise in their editorial will need to be addressed.

Cheung is a consultant for Neovasc. Anyanwu reports no conflicts of interest related to the study. Adams is the national coprincipal investigator of the US Medtronic CoreValve trial. The Icahn School of Medicine receives royalties for intellectual property related to mitral- and tricuspid-repair products from Edwards Lifesciences and Medtronic.

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