When Earl Bakken started Medtronic back in 1949, little did he realize that his pioneering work in electrical heart pacemakers would spawn a vast industry whose devices would save millions of lives and improve the quality of life of millions more (see "A Short History of The Pacemaker," p. 54). Today, Medtronic enjoys worldwide leadership in a variety of medical products and services, many of which trace their roots to the cardiac pacemaker. Its revenues in the year ended April 25, 2003 were $7.665 billion, nearly half of which are derived from pacemakers and defibrillators (which also contain pacemakers) to treat a variety of ailments.
Cardiac pacemakers provide electric signals to the heart to make it beat properly when the heart's own natural pacemaker fails. Failure can occur due to blockage of the heart's natural electric signals, an ischemia (decreased flow of oxygenated blood to an organ due to obstruction in an artery), or a myocardial infarction (destruction of heart tissue resulting from obstruction of the blood supply to the heart muscle). The electronic pacemaker senses the heart's own rhythm and sends a correcting signal when needed. The pacemaker is implanted under the skin, most often just under the collarbone (Fig. 1).
After the pacemaker was developed, implantable defibrillators came along. Unlike pacemakers, which generally put out a train of 0.5- to 8-V (4 V nominally) pulses, defibrillators "shock" a failing heart into action with 750-V pulses. Over time, the defibrillator was combined with a pacemaker, and it's now called an implantable cardioverter defibrillator (ICD). All defibrillators made today contain a pacemaker (Fig. 2). Heart disease is the leading cause of death in the U.S., and many of these deaths can be attributed to irregular heartbeats, which pacemakers and defibrillators are designed to alleviate.
Mention pacemakers and most people think of cardiac applications. Although heart stimulation was the original application, pacing technology has gone far beyond cardiac applications. The newest uses include pain management; the control of essential tremors and Parkinson's disease; the treatment of seizure disorders, sleep apnea, and epilepsy; and bladder control. Pacemakers now interface with the spinal column, the brain, and the abdomen, in addition to the pectoral region of the chest, where they're typically implanted for cardiac applications.
One advanced medical device spawned by the pacemaker is Medtronic's Chronicle, an implantable cardiac monitor that may revolutionize the advanced detection and treatment of heart problems. It provides physicians with readings of the heart's workings, enabling them to modify cardiac therapy by adjusting programmable pacemaker or defibrillator operation or by altering medications.
Chronicle is currently being tested in a clinical study of about 300 patients. If all goes well, it could be on the market in 2005. This device will add to the company's expanding monitoring device business, launched in 1998 with the release of the Reveal syncope monitor (syncope is a spontaneous loss of consciousness caused by insufficient blood to the brain).
"One of the most promising and exciting new areas for the cardiac device industry is implantable monitors," says Ed Duffin, director of Medtronic's Heart Failure Research Group. "These devices provide objective information that should help the physicians to be more successful in managing therapy."
Pacemakers are no longer standalone devices. The momentum for remote patient care has brought about the development of Internet-based systems that cost-effectively expand the scope of patient-care coverage. Early last year, for example, Medtronic introduced its CareLink network, which lets physicians manage more patients with implanted devices via the Internet.
"The physician gives the patient a small remote monitoring device to use at home. That unit interrogates the implantable device and sends, via the Internet, information to the physician for examination," explains Duffin.
All modern implantable pacemakers contain an input sense amplifier, a microprocessor, a sensor, some memory to store programming code, a transceiver circuit to allow monitoring and programming via an external telemetry loop, a pulse generator, and a power supply, all powered from a single small battery. Reliability, extremely low power consumption, and small size are critical design issues for any implantable pacemaker and defibrillator. The sensing element in the pacemaker is usually a microelectromechanical system (MEMS) accelerometer, which monitors the patient's physical activity.
Because an implantable device and the thin wires (leads) connecting it to the heart are placed in the human body in an environment that's very hostile, and since 10 years of reliability are mandated, the device's behavior must be well understood. Such a task requires sophisticated mathematical modeling and simulation. Medtronic's large and active Materials and Modeling Group specifically works on these issues. It does so for all of its medical products, including pacemakers, using the latest modeling and simulation techniques.
In their continuing quest to reduce pacemaker and defibrillator power levels, designers at Medtronic's Bakken Research Center in Maastricht, the Netherlands, working with designers at Delft University, also in the Netherlands, recently developed an ultra-low-power sense amplifier that operates from just 2 V and dissipates a mere 240 nW. Operating on a dynamic-translinear (DTL) circuit, it comprises a voltage-to-current converter, a bandpass filter, and absolute-value rms-dc converter and comparator circuits (Fig. 3).
The designers are proposing analog usage of the wavelet transform, via the DTL circuit, to further reduce power requirements. They point out that a fully integrated analog QRS complex detection circuit can be built to operate from a 2-V supply and dissipate only 55 nW/scale. The QRS complex comprises the deflections in an electrocardiographic tracing, representing ventricular activity of the heart.
Given such low-power requirements, it's not surprising that you won't find any commercially available high-speed and high-power microprocessors. Instead, all that's needed is a microprocessor that performs its bare minimum functions to keep the heart in rhythm when cardiac levels go below or above a person's normal heart rate.
Medtronic prefers to design its own custom microprocessors, which generally need to draw no more than a microampere or two and operate from 1 or 2 V. The company previously patterned its microprocessor designs after the 16-bit RCA 1802 and Motorola 6805 microprocessors. Although the devices continuously monitor the heart, the idea is to keep the microprocessor in a "sleep" mode until the sensor recognizes a problem and wakes it up so the device can keep the heart beating in rhythm. Then, it goes back to sleep.
Early on, pacemaker microprocessors stimulated the heart at preset rates and kept on working as long as the heart rate fell below or went above the preset rates. Physicians can now program newer versions via a closed telemetry loop to act on tighter preset rates to save even more power. This means smaller amounts of memory code space are stored in an onboard ROM, which generally doesn't go much above 16 kbytes.
Cardiac pacemakers have a wide range of parameters that can be set by the physician. These include the pacing rate, the timing between the upper and lower chambers of the heart, the timing between pacing of the heart's left and right ventricles, the pacing output energy, and the pacemaker's monitoring capability.
Extremely limited memory requirements, though, can present a challenge to writing an operating system, which is usually small. The operating system is generally written in assembly language.
Mercury-zinc batteries powered nearly all of the early implantable pacemakers. However, their average lifetime was only about two years. Failed batteries caused some 80% of implantable pacemaker failures during the 1960s. Clearly, a more reliable power source was needed.
Wilson Greatbatch, inventor of the implantable pacemaker, got to work. After licensing the implantable pacemaker to Medtronic, he spent several years experimenting with various kinds of batteries, including nuclear and rechargeable. In 1968, he developed the lithium battery (see "A Short History of The Pacemaker," below, again). James Moser then developed an improved version, the lithium-ion battery, which offered a 10-year lifetime. Greatbatch incorporated this newer version in his designs. Medtronic now makes its own batteries.
Scientists at Medtronic constantly look to expand the use of the pacemaker for cardiac as well as noncardiac applications. One such example is the aforementioned Chronicle implantable device, which monitors cardiac hemodynamics and arrhythmias, as well as patient activity levels.
Toby Markowitz is a Distinguished Scientist in Pacing Research at Medtronic and an electrical engineer with a sound knowledge of biomedical engineering issues. He stresses the importance of understanding the human body's electrical network. "With all the nerves in the body, there's a large amount of electricity flowing around that controls many functions," he says. "Understanding control-system theory from an engineering perspective is very helpful to understanding human physiology. There are lots and lots of closed-loop control systems in the body which can be modeled. Understanding their impulse response is critical."
"Electrical pacing, the building blocks of pacemaker technology, is also being used in a variety of noncardiac neurological applications," says Mark Rise, Senior Principal Scientist for Medtronic's Neurological Ventures Organization, which was formed during the 1970s for such applications. "A pacemaker is an implantable electronic device with a lead wire connected to the tissue of the heart. It provides stimulation pulses about 70 times per minute. That same kind of technology now goes into a neural stimulating device that's interfaced with the spinal cord, a peripheral nerve, or in some cases implanted in the brain and typically stimulates these locations from 15 to 185 to 250 times per second."
Much of this noncardiac neurological stimulation is based on a new understanding of how the human nervous system works and how it relates to treating chronic pain, known as the 1965 Melzack and Wall Gate Control Theory of pain. Canadian psychologist Ronald Melzack and British physiologist Patrick Wall suggested that the spinal cord contains a gating mechanism that closes in response to normal stimulation of fast-conducting, large "touch" nerve fibers. However, that gate opens when the slow-conducting small "pain" fibers transmit high-volume and intense sensory signals. The gate could be closed again if renewed stimulation of the larger fibers counters these signals.
"That new physiological understanding was leveraged into a technique to alleviate those indigenous pain-control mechanisms we have in our nervous system by electrically stimulating the spinal cord itself," says Rise. "During this same period of time, there were also minor variations of this technique for stimulating locations deep within the brain to ease pain."
This spurred on the development of ways to treat motor symptoms of Parkinson's disease, dystonia (chronic activity of particular neural circuits that leads to overcontraction of certain muscles, making normal movement sometimes impossible and even painful), and epilepsy. "We're in the process of launching a pivotal trial to stimulate a region of the thalamus called the anterior nucleus, which is part of the circuitry that's involved in a large portion of those who have seizures," says Rise. "It connects to the temporal lobe with portions of the brain, which when stimulated can prevent the onset of seizures."
Medtronic has produced the Activa, an implantable neurostimulator for the control of Parkinson's disease, which it describes as "one of the most significant and innovative advances in the treatment of Parkinson's disease in more than 30 years." This system consists of three parts: a thin insulated coiled wire, with four electrodes at the tip, that's implanted in the brain; an insulated extension lead that's threaded under the skin, from the head, down the neck, and into the upper chest; and a neurostimulator that connects to the extension and is embedded beneath the skin into the chest (Fig. 4). It not only can be used to stop severe tremors, but it also has gotten patients with advanced symptoms to walk again, feed themselves, and regain lost levels of activity.
Another new application for the pacemaking principle is stimulation of the sacral nerve roots to help control bladder dysfunction. Incorporated into Medtronic's InterStim device, this therapy manages urinary retention and symptoms of an overactive bladder. The device is usually implanted in the abdomen near the bladder (Fig. 5).