On the Radar…

In 1880 Thomas Edison patented the electrical fuse in order to intentionally create a weak link in the wiring of his newly invented artificial light strings. Edison believed that in the event of electrical overload it was best to isolate the location of stress for both safety and convenience, so when the system became disrupted it was simply a matter of a trip to the fuse box instead of tearing out the walls looking for failed wire. Dr. Ivan Vesely, the founder and chief scientific officer of ValveXchange Inc. has deployed similar genius in approaching the replacement of heart valves. Presently, after an initial surgery to replace a patient’s faulty valve, there is some likelihood the new prosthetic valve will itself need replacement within the patient’s lifetime. This requires cracking open the chest and going on a cardiopulmonary bypass pump a second time, a procedure of considerable risk and trauma for what is likely a geriatric patient. Vesely’s company ValveXchange offers a less invasive alternative: By installing a “docking station” for the prosthetic valve during the initial surgery, replacement tissue valve could be swapped out at a future time more easily and potentially without sawing through a patient’s sternum. While perhaps not as simple as a trip to the fuse box, ValveXchange possesses the potential to fundamentally alter the valve replacement treatment paradigm.

Over 100,000 patients in the United States undergo heart valve replacement procedures each year. Valve replacement is a major surgery resulting in sometimes severe complications and significant recovery time. Patients are currently faced with two less than optimal options: tissue or mechanical replacement valves. For patients over 65 or with limited life-expectancy, surgeons often opt for tissue valves, which are of animal origin. While this type of replacement most closely mimics the original valve, these valves can wear out after 15 to 18 years. When this happens, a patient must undergo the same open-heart procedure to replace the worn valve.

For younger patients, implantation of more durable mechanical valves may be preferred. While these valves last longer and thus decrease the likelihood of re-operation, a key disadvantage is the associated high potential for blood clots which requires patients to receive anticoagulation therapy, most commonly warfarin (brand name Coumadin), for the rest of their lives. Warfarin is a notoriously hard medication to manage as patients can react very differently, making it difficult to keep patients in the therapeutic range. Optimal management requires patients to make significant lifestyle changes including undergoing regular blood tests to monitor INR levels, avoiding many medications and supplements, following a limited diet and avoiding any activities that would risk injury and uncontrolled bleeding

Vesely, a renowned valve researcher, had the feeling in 2000 that “improvement in durability [for tissue valves] had really plataeued out,” making it unlikely a new tissue valve will last more than the standard 15 to 18 years. The next best thing to a longer lasting valve is one that is easily serviceable – the concept which came to Vesely in the middle of the night and is at the core of the ValveXchange system. Under the ValveXchange system, a patient’s intitial heart valve operation proceeds in much the same way as under the other two methods – but there is a substantial difference in the hardware implanted. The ValveXchange apparatus consists of two distinct parts, a docking station which is sewn into place (holder) and an exchangeable tissue-based leaftlet set (the actual valve component would match the off-patent industry standard -Capentier-Edwards set). One advantage of this surgery is that the delicate leaflet set can be kept safely in the jar while the holder is sewn into place making the suturing process faster.

In the event the tissue valve set failed, there would be a “range of procedures” that physicians could opt for to replace the valve, all of which offer advantages over the traditional procedure. Vesely explains “even with conventional surgery [exchanging the leaflets rather than completely replacing the valve] would minimize the time on pump.” The company is also developing thin tools that could allow the surgery to be conducted via a small incision between the ribs either on or off pump which eliminates the trauma of opening the sternum.

The question remains to whom exactly this product would be most attractive as there are potential benefits all patients. For patients over 65 (about 60% of surgeries based on 2006 data from the HCUP Nationwide Inpatient Sample) who would likely have otherwise received a tissue valve under normal surgical procedures, ValveXchange offers an “insurance policy” against the possibility that they will outlive the valve implanted. For patients with longer life expectancy who are currently more likely to receive mechanical valves, this system offers a freedom from warfarin – and an annual morbidity rate of 2-3% associated with the drug – without having to face a second surgery as invasive as the first in the event of valve failure. It is this population of young, active patients that would otherwise receive mechanical valves who Vesely believes will be the initial customers for his company’s products.

In the push towards getting the ValveXchange system to market, Vesely is joined by CEO Larry Blankenship, who most recently served as CEO of Cardio Optics. In July, the company secured a $1.6M SBIR grant from the NIH which they hope will take them through further design refinement and some animal testing. The company hopes to raise $6M in additional capital in 2009 to take it through the extensive preclinical testing the FDA requires for heart valves. Upon completion, Vesely thinks that the company would be an attractive target for any of the big three heart valve makers – Medtronic and Edwards the leaders in tissue valves, or St. Jude the leader in mechanical valves. If acquisition does not occur, the ValveXchange team has the expertise to go into human trials, but would require additional capital at that point.

While replacing a heart valve a second time will likely never become as simple as a trip to the fuse box, the ValveXchange system is revolutionary in its attempt to identify the weak link and enable serviceability. In today’s world, one would be considered quite mad if they decided to rewire an entire house due to a blown fuse. Maybe ten years from now traditional re-operations, with their attendant risks and complications, will seem just as strange.