1 September 2001

Replacement heart begins clinical trials

by Bob Felton

Industry-proved sensors and materials combine to save lives.

Clinical trials of an electric-powered, grapefruit-sized pump that may someday serve as a permanent replacement for diseased hearts commenced 2 July with implantation of the device in a terminally ill cardiac patient at Jewish Hospital in Louisville, Ky. More than 20 years in development by Danvers, Mass., bioengineering firm Abiomed, the implantable replacement heart is the first of several expected to come to market in the next few years-just as the number of Baby Boomers appearing in emergency rooms with chest pains is expected to increase.

Those unfortunates who must undergo heart replacements will be relying in large part on technological advances road tested for the past 20 years in manufacturing plants worldwide.

Abiomed's implantable pump, the AbioCor, exploits the advances in sensing, miniaturization, and computer control of the two decades elapsed since trials of the Jarvik-7, the first artificial heart, in 1982. Weighing in at 2 pounds and about the size of a grapefruit, it fits inside the chest cavity and wholly replaces the diseased heart. A battery worn on the patient's belt provides power; an attached transmitter sends a signal to a coil implanted just below the patient's skin, which in turn sends power to the pump. There is no direct mechanical connection between the pump and anything positioned outside the patient's body, minimizing the risk of infection that plagued Barney Clark, the first artificial heart recipient (see sidebar).

In addition to powering the heart, the system charges a backup battery that operates the pump for up to half an hour—time enough for patients to take a shower or otherwise shed the battery pack.

Replaces 'Fight or Flight'

When the brain perceives a threat, it sends a command to the adrenal glands to begin dumping epinephrine—adrenaline, a hormone that tells the heart to accelerate in order to run or do battle—into the bloodstream.

Instead of relying on chemical sensors to detect epinephrine, the designers chose instead a miniature pressure sensor that continuously monitors blood pressure. When the sensor detects increases of the inflow blood pressure, it sends the data to an algorithm embedded on the controller microprocessor, which regulates the pump speed. This setup allows the pump, with a very modest lag time, to respond to user demand.

Ordinarily, our hearts race when we're confronted by a threat—an aggressive animal, for instance. By the time we begin running, even if only instants have elapsed, the heart has already geared up and gone into overdrive to carry the added load. For the AbioCor user, demand drives acceleration: Begin running, and the pump's onboard electronics will figure out it needs to work harder.

Almost the Real Thing

The human heart consists of two halves separated by a muscle called the septum. Each half has an upper and lower chamber, known as the atrium and ventricle, respectively. Blood enters the heart via the atrium on the right side and exits via the ventricle. On the left side, returning blood enters the heart through the ventricle and exits via the atrium. The AbioCor pump closely mimics the architecture of the heart, replacing the septum with a resilient membrane that houses gel and a small motor.

The pump simulates the action of a human heart by pumping gel first to one side of the membrane and then to the other. The hydraulic pressure in the blood on the adjoining side of the heart increases as the gel moves to one side, forcing it to flow through one-way valves. The reciprocating motor forces gel to the opposing side of the septum; once again, the hydraulic pressure increases, and the blood begins flowing in the opposite direction. The AbioCor circulates up to 10 liters of blood per minute, enough to allow its user to make a vigorous trip up a flight of stairs, play some low-intensity tennis, or join in a pickup basketball game in the driveway.

Though conceptually straightforward, the engineers confronted problems that have few analogs in conventional mechanical design. First, red blood cells are susceptible to damage from passage through the pump. To prevent that, designers adopt one of two strategies: The interior of the pump may be lined with a carefully textured surface that captures red blood cells and promotes creation of a film that shields flowing cells from damage, or the interior wall may be made extremely smooth.

The AbioCor designers opted for the second alternative, selecting a titanium and plastic construction so smooth that delicate cells slide along the walls unaffected. The second problem is that still blood tends to clot—a potentially fatal flaw if the pump harbors dead zones where there is no movement. Additionally, shielded from constant intermingling with white blood cells, such zones may become breeding grounds for bacteria. Accordingly, the flow route has no ridges, corners, or sharp turns—a slick trick, given the small space the designers had to work with.

Uncertain Future

The Food and Drug Administration has so far approved five implantations, and the full clinical trial will probably consist of 15-20 implantations performed by teams at five different hospitals over the course of two to three years. Though the thoracic component of the pump will remain constant during the life of the trials, Abiomed engineers might make some modifications to the system toward the end of the trials if the data warrants it; the power assembly has performed as required, for instance, but designers now think it can be improved.

The immediate design goal is a pump that lasts a minimum of five years, the average life expectancy of a heart transplant recipient. The pump connects directly to the recipient's blood vessels, with the sutures wrapped in a Dacron cuff. The designers speculate that it will someday be possible to remove and replace worn-out pumps.

If they have them, that is. Presently, Abiomed estimates that roughly 100,000 people a year could benefit from installation of the pump. Further, the aging Baby Boomers will probably drive that number up sharply in the next decade. But at present, Abiomed technicians build and test virtually every pump by hand. The company is currently studying a transition to large-scale production in anticipation of successfully completing the clinical trials and winning authorization for commercial development. IT