The American Heart Assn. says one in three deaths in the Western world is caused by heart disease. With only 20,000 transplant hearts available each year, new treatments should be well received. This cardiac market has large revenue possibilities and the potential to grow, by some estimates, over $10 billion by 2013.

Stem cell and tissue engineering have applications covering a wide range of diseases and their use may yet radically change medicine. Stem cells are undifferentiated cells that can develop into specialized cells if properly triggered. But a few level-headed researchers caution that the wide-eyed predictions common in the general media are still many years off because of the complexities involved. Until then, look to devices that are here and now - the heart pumps, artery cleaners, and new ideas in pacemakers - to give the heart a hand.

Kid-friendly devices

Kids are smaller than adults and they grow fast. That obvious observation, common to most parents, has apparently escaped many device designers and led surgeons to implant small-adult items into children. But this leads to complications such as the need to make adjustments to the devices in the OR when time is critical. But device makers are fianlly coming around.

Device firm Berlin Heart Inc, Northborough, Mass. (www.berlinheart.com) has begun marketing its E.U.-approved heart pump for infants in the U.S. The Excor Pediatric Ventricular Assist Device is under investigation in an IDE clinial study to gain FDA approval.

Berlin Heart VP of Clinical Affairs Bob Kroslowitz says the pump will be available in six sizes when it is approved. The smallest, a 10-ml-stroke volume, is for infants while the largest, with an 60-ml stroke volume, is for larger children. “The heart pump works outside the body with its cannulas inside. It can be used for univentricular or biventricular support, that is, to support the left ventricle independently or left and right at the same time. The pump has blood and air chambers separated by a triplelayer polyurethane membrane and is driven by an electro-pneumatic unit. A graphite layer between each polyurethane layer reduces friction as they move back and forth,” he adds. The ventricular assist device (VAD) is primarily used as a bridge-to-transplant unit, meaning it keeps the patient alive until a donor heart is available.

The Excor VAD is said to protect against thrombogenesis - clot formations - with heparin coatings and smooth inner surfaces on blood chambers that also ensure best possible flow characteristics. Titanium fittings between pump and cannulas ensure good connections.

The pumps are made from a clear polyurethane that allows permanent visual inspection and makes it easy to monitor membrane movement and assess the device function. The pump comes with one of two valve designs, a tilting disc or a tri-leafelet polyurethane-velum valve. The pediatric version uses the tri-leaflet polyurethane valves to promote unidirectional flow through the pump. Valve and pump surfaces of the Excor Pediatric that contact blood are of the same material. And a de-airing port makes it easy and safe for surgeons to remove air pockets after connecting the pump to the cannulas.

Another left-ventricular assist device, the DuraHeart from Terumo Heart, Ann Arbor, Mich. (termuomedical.com), uses magnetic levitation to eliminate contact between impellor and blood-flow path, thus minimizing chances of mechanical failure.

The company says magnetic levitation prevents many problems associated with similar systems that rely on a pressure distribution to suspend the impeller. When those systems start for the first time, the impeller, just sitting on the bottom of the blood chamber, can scratch the chamber surface and potentially create a source for cells to start clotting, according to Terumo Heart's Mark White. In addition, the outside forces from vigorous activity could perturb the impeller, causing flow variations and even areas of stagnant flow. “It is difficult for hydraulics alone to keep the impeller centered, so if a patient is doing something active, it's conceivable that a bump could deflect the impeller enough to touch the chamber wall,” he adds.

The DuraHeart, on the other hand, uses X, Y, and Z-axis position sensors and a controller to keep the impeller centered in the chamber, allowing for a relatively large gap between impeller and chamber wall. Regardless of what happens on the outside, the impeller never drifts out of position. “The improved flow minimizes shear stress and eleminates stagnation points, which can let clots form. White has seen no problems with blood clots in DuraHearts that have been removed from patients.

The impeller, pump, and inflow conduits are made from a titanium alloy. The outflow conduit is made of Vaskuteck Gelweave, a proprietary, sealed, polyester graft with a gelatin coating that eliminates the need to preclot, or coat, the graft during surgery, thereby cutting OR time.

Patients wear a small battery-powered controller. It has a small screen to display pump flow and rotational speed, set point, motor current, and notify patients of alarms and alerts. The controller communicates with a hospital console for setup, monitoring, follow-up, and troubleshooting.

The DuraHeart has been used in more than 70 patients in Europe, with the longest being more than three years. White says the permanent-LVAS market is bigger than the bridge-to-transplant market because there are only about 2,000 donor hearts annually available in the U.S. and about twice that are on a waiting list.

Another pump manufacturer, HeartWare, Farmingham, Mass., (heartware.com) reports that a U.S. patient has received its LVAS at Washington Hospital Center, for the start of its U.S. trial. Model HVAD also uses a magnetically levitated impeller. The company has designed at least two pumps, each smaller than earlier generation devices. Even the larger HVAD is small enough to fit directly adjacent the heart in the pericardial space.

Two small motor stators inside the pump housing turn the impeller. A driveline (cable) exits the patient through the skin and connects to a controller. This battery-powered unit includes an adaptor so it can run on household current or from a vehicle power outlet. The controller operates the pump and provides patients with signals and alarms. Controller and batteries are in a carrying case that can be worn either on the patient's belt or over the shoulder.

Mending defective hearts

A novel tissue-removal tool, just 2.5-mm wide and less than 1-mm high, is intended to help with pediatric heart repairs. And if researchers can make the proof-of-concept device smaller, surgeons will be able to repair several maladies to a baby's heart while it is still in the womb.

The tool is part of a program to develop instruments and procedures based on miniature instruments attached to the end of steerable needles for cardiac procedures. Such operations usually required open heart surgery, a complex task that calls for halting a beating heart. “This ambitious program builds on two recent developments,” says Adam Cohen, CTO for Microfabrica Inc., Van Nuys, Calif. (microfabrica.com). “One is our method for making tiny working instruments and implants smaller than previously possible, and a steerable needle, a device developed at Boston University.”

Doctors have long been able to get inside the body using a catheter, but more than an unguided catheter is needed to move controllably along a trajectory, especially where there is no guidance from a blood vessel, and into an open cavity such as the heart. The job calls for a shape that can change, like a snake. Engineers at BU are developing such a device with coaxial Nitinol tubes preformed into different shapes, some straight and some curved. When assembled, they generate predictable and useful shapes that allow steering a device at the tip so it gets to the right place,” say Cohen.

Microfabrica's Efab method for making parts builds them layer by layer and works with at least one structural material and a sacrificial material that serves as scaffolding during part construction. “Our current research is focused on finding an implantable material and techniques that reduce the size of clearances between moving elements,” says Cohen.

“The design of the tissue-removal tool separates the teeth from the drive end using a gear train because we want to plunge deeply into tissue,” he says. Holes on the top and bottom let the sacrificial construction material inside the gear box escape in a post-manufacture operation.

The target ailment is a congenital heart defect called Tetralogy of Fallot. “It's four defects rolled into one and affects children. Normally it's corrected by one or more surgeries shortly after birth. The goal here is to do it less invasively. One defect, for example, is that blood from the right ventricle going into the lungs is partially blocked below the valve. Our device will nibble away at the unwanted muscle and avoid open-heart surgery. One challenge is to get through two types of tissue. One, the endocardium or lining of the heart, is quite tough and elastic. The other, the myocardium or a heart muscle layer, is thicker but softer,” says Cohen.

“We don't yet know how well it will do on endocardium, but initial tests on myocardium are promising. Other tests will be conducted at Children's Hospital Boston on pig hearts.”

As it turns out, there is also a condition in which it is useful to have a hole in a developing heart. Without it, the heart cannot develop properly, giving rise, for example, to hypoplastic left heart syndrome. One current practice is to make a hole with a needle and balloon. But because it does not remove tissue, the hole collapses soon after because the tissue is quite elastic. “So we'd also like to make a hole in the septum of the heart that does not close up.”

Cohen says the size of the device in the accompanying picture works well according to the company's Efab design rules. “But it could be made somewhat smaller or larger as needed. If it is to target fetal heart surgery, it must get through an 18-gauge needle that will go through the uterus without causing premature labor. So the design might change,” says Cohen.

Pacemaker knows best

Engineers are designing pacemakers into smaller packages. The Reply series of dual and single chamber pacemakers, for example, from the Sorin Group, Italy, each occupies only 8 cc, making them the smallest pacemakers available, according to the company. The device is approved for use in the E.U. and U.S.

Sorin engineers say the Reply selects between two pacing modes in normal operation, with sensors detecting which mode would be most useful at any instant. Switching from the AAI pacing mode (atrium paced and sensed, inhibited trigger) to DDD mode (dual (atrium and ventricle) paced and sensed, but atrium triggered and ventrical inhibited) in case of AV (atrioventricular) block detection, reduces unnecessary pacing. And studies show that unnecessary pacing to the right ventricle increases the risk of heart failure and atrial fibrillation. The pacemaker also includes a feature which lets users automate follow up tests and provides data reporting and recommendations.

A tool for repairing broken hearts

The tissue removal tool is for heart surgeries. It is one of the devices built as part of Microfabrica's participation in NIH-sponsored research for developing instruments and techniques for minimally invasive heart surgery. Patients will range from fetuses to adults. The tool contains 11 gears and six sharp counter-rotating blades, which spin at thousands of rpm. The device is 2.5-mm across and about 0.7-mm thick. The company's Efab process can produce hundreds of units identical in dimensions and tolerances on a single wafer. The device needs no post-processing assembly.