With any new medical treatment, there are two types of risks: those that are known and anticipated from precommercial clinical work, and those that are unknown, can’t be predicted and only emerge once a device or procedure is exposed to real-world clinical practice. New products and procedures start out by being vetted in the protected, false security of clinical trials, involving small numbers of hand-picked patients often treated by leading physicians under ideal circumstances. Only as real-world clinical experience accumulates in large numbers of patients with a multitude of unpredictable comorbidities and complications do the unanticipated problems begin to emerge.
That’s where TAVI (transcatheter aortic valve implantation) is today. Minimally invasive transcatheter treatments for the aortic valve as an alternative to surgical valve replacement have been available in Europe since 2007 (and in the U.S. since November 2011), and in recent years the number of procedures in Europe has more than tripled, according to a presentation made at this year’s EuroPCR interventional cardiology meeting in Paris in May. Dr. Nicolo Piazza of the German Heart Center (Munich, Germany) noted that for Europe as a whole, TAVI procedures numbered 4,498 in 2009, 14,599 in 2010 and 18,372 in 2011. To date, an estimated 50,000 patients have been treated in 46 countries. That’s enough time and experience for the cracks in the new procedures to start to show.
The most serious problems to emerge include vascular and bleeding complications, stroke and paravalvular leaks. Innovators in the field, like Edwards Lifesciences Corp., the first on the market in Europe and the US, Medtronic Inc.’s Medtronic CoreValve LLC, which has TAVI products on the market in Europe, and numerous emerging companies are devoting lots of energy to the improvement of prosthetic valves and their delivery systems. These companies are looking to optimize valve design with the goal of minimizing the trauma the devices cause in the vessels on the way to the heart, or are crafting ways to position them better in the native annulus of the aortic valve. JenaValve Technology GMBH and Symetis SA, for example, believe they’ve grabbed second-generation advantages with valves that self-position and can be repositioned. Clinicians believe that better valve positioning will reduce paravalvular leaks. Colibri Heart Valve LLC is developing a smaller device, an atraumatic low-profile foldable aortic valve that can be delivered through a 14 French (14F) procedural sheath. Today, sheath diameters for current transcatheter heart valves range from 18F to 24F. A smaller device is easier to navigate through vessels, and theoretically causes less damage in very sick patients with fragile, thin, tortuous, or calcified vessels. For the start-ups developing these next-generation technologies the real question may be: Will clinicians prefer that the heart valves be revised to provide better access, or will they prefer a new method of access?
More than a dozen companies developing devices for access site management answer the latter in the affirmative. Their thesis is that new access devices can improve outcomes and bring more patients to minimally invasive treatments for structural heart disease.
One group of companies is working on vascular closure devices for large-bore procedures, that is, the delivery of large-diameter devices in the range of 12-24F. (The conventional balloons and stents of interventional cardiology can be delivered through sheaths 5-8F in diameter.) Large-bore procedures result in sizable wounds and overstretched vessels that will not close by manual compression, which is still the gold standard means of closure for small-bore procedures. This group includes Abbott Laboratories Inc., AccessClosure Inc. (a leader in small-bore vascular closure now developing a large-bore closure product), Promed Ltd., VivaSure Medical Ltd. and VasoStitch Inc.
The other group is targeting a newer access method, the less developed transapical procedure where the chest and apex of the heart are punctured to allow access to the left ventricle. The first products of Apica Cardiovascular Ltd. and Entourage Medical Technologies Inc., profiled in this issue, fit into this category, as do those of NovoGateMedicalLtd. and Micro Interventional Devices Inc.
As the long list of start-ups suggests, any truly successful new therapy will bring with it more products than just a single type of therapeutic implant (in this case the transcatheter heart valve). Michael Whitman, president and CEO of Micro Interventional Devices, says, "Whenever there is a disruptive or transformative technology, there is often a need to create peripheral devices around it to support it." MID plans to take advantage of the short and straight path to the heart that is available through the apex to enable a range of treatments for structural heart disease. (See Micro Interventional Devices: Creating A Tool Box For Structural Heart Disease, IN VIVO, June 2012.)