In the fall of 1960, Greatbatch and Chardack licensed their implantable pacemaker to a small Minneapolis company called Medtronic, which had been started by Earl Bakken, an electrical engineer who worked with Lillehei. Production began almost immediately. By the end of the year, the company had orders for fifty pacemakers at $375 apiece. Greatbatch continued to work on the device, testing transistors and other components in two ovens and a workbench set up in his bedroom in upstate New York. (The U.S. Minuteman nuclear missile program subsequently adopted many of Greatbatch’s quality-control measures.) The demand for cardiac pacemakers quickly skyrocketed. Approximately 40,000 units were implanted in 1970 and about 150,000 in 1975. Today there are more than one million units in use around the world. In 1984, the National Society of Professional Engineers selected the implantable pacemaker as one of the ten most important engineering contributions to society over the preceding half century and honored Wilson Greatbatch, the humble engineer from upstate New York, as its inventor.
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In addition to complete heart block, a deadly-slow arrhythmia, the other great problem cardiac electrophysiologists were grappling with at mid-century was ventricular fibrillation, the fast arrhythmia that was responsible for most sudden deaths across the world. At the turn of the century, Jean Louis Prévost and Frédéric Battelli, two researchers at the University of Geneva, discovered that electricity could be used not only to provoke ventricular fibrillation but to tame it as well. They were able to induce fibrillation in animals with relatively weak alternating current and then terminate it with a much larger “defibrillatory” jolt, resetting the heartbeat. Decades later, in 1947, the American surgeon Claude Beck successfully used electrical defibrillation for the first time in an operating room, on a fourteen-year-old boy at the Case Western Reserve University Hospital in Cleveland who went into cardiac arrest following a chest operation. The boy survived to be discharged from the hospital. Beck later wrote that defibrillation was a tool for saving “hearts too good to die.” He envisioned the therapy as being “at the threshold of an enormous potential to save life.”
As was the case with electronic pacing, externally applied defibrillation came first. In 1956, Harvard’s Paul Zoll, who also pioneered external pacing, performed the first successful external defibrillation in a human subject. Other scientists, most notably William Kouwenhoven, a professor of electrical engineering at Johns Hopkins, also made seminal contributions. Kouwenhoven worked on external defibrillation for decades, mainly in rats and stray dogs. By 1957, he had assembled a defibrillator in his research lab on the eleventh floor of the Johns Hopkins Hospital. That March, a forty-two-year-old man arrived in the emergency room at two o’clock in the morning complaining of indigestion. He was actually having an acute myocardial infarction, and while undressing, he collapsed in ventricular fibrillation. The admitting resident, Gottlieb Friesinger, had heard about Kouwenhoven’s defibrillator and raced upstairs to get it while an intern attempted to resuscitate the patient. Friesinger persuaded a security officer to let him into Kouwenhoven’s lab, where he picked up the hefty device, nearly two hundred pounds, and wheeled it to the ER. With one electrode at the top of the breastbone and another just below the nipple, he delivered two shocks to revive the dying man. It was the world’s first successful emergency defibrillation for cardiac arrest.
Kouwenhoven’s research produced an unusual and unexpected side benefit. In experiments on dogs in the late 1950s, Guy Knickerbocker, a graduate student in Kouwenhoven’s lab, noticed that blood pressure rose slightly when defibrillator paddles were pressed into position, even before any electrical current had been administered. Collaborating with James Jude, a surgeon, Knickerbocker showed that pressing on the chest can compress the heart and cause blood to temporarily circulate, thus increasing blood pressure. His observation set the stage for the introduction of chest compressions during cardiopulmonary resuscitation, the standard treatment used today. Within a year, this technique was being taught to firefighters and other rescue personnel. The discovery, serendipitously, benefited Knickerbocker personally. In 1963, his father underwent successful CPR during cardiac arrest after a heart attack.
External defibrillators quickly proliferated in the new cardiac care units of the 1960s. The machines were at the ready to treat the arrhythmic disturbances of heart disease, if not the disease itself. Monitoring in these units confirmed that ventricular fibrillation was the most common cause of cardiac arrest and sudden death. In 1961, a group led by Bernard Lown at Harvard incorporated a timer to synchronize the defibrillator with an EKG to avoid delivering shocks to the heart during the vulnerable period.
But as was the case with pacemakers, external defibrillators were unwieldy, and the shocks they delivered—in the rare cases when patients were still conscious—were painful. Moreover, they relied on bystander administration, hardly infallible during an emergency. Therefore, as with pacemakers, the goal became to miniaturize, automate, and implant them inside the body.
Though several groups were involved in the invention of external defibrillation, only one, led by Michel Mirowski at Sinai Hospital in Baltimore, was responsible for the creation of the implantable defibrillator. As a Jew born and raised in Warsaw, Mirowski led a peripatetic life. In 1939, as an adolescent, he left his family and fled his country after the German invasion and occupation of Poland. (He was the only member of his family to survive the war.) He ultimately returned to Poland. After the war, he did his medical training in France. A Zionist, he eventually moved to Israel. In 1966, when he was already a practicing cardiologist, he experienced a life-changing tragedy when his close friend and mentor, Harry Heller, died of ventricular tachycardia, a malignant rhythm that is often a precursor of ventricular fibrillation. Like so many traumatized by sudden cardiac death, it became his lifelong obsession.
In 1968, Mirowski moved to the United States. As chief of the new coronary care unit at Sinai Hospital, he negotiated time to pursue his own work in the basement of the hospital’s research building. His project, conceived in Israel after Heller’s death, was to build an implantable defibrillator. Mirowski paired up with Morton Mower, another cardiologist, and together they created a blueprint for the device. Mirowski knew that a strong electrical shock was needed to terminate ventricular fibrillation. However, he believed that with external defibrillation, most of this energy was wastefully dissipated in the tissues around the heart. He wondered whether the discharge of a simple capacitor, an electronic element that stores charge, might be sufficient to terminate fibrillation if the capacitor was in direct contact with the heart. Working with engineers, Mirowski and Mower designed circuitry to detect ventricular fibrillation and trigger the charging of a capacitor by a battery. The challenges were enormous: miniaturizing the circuits, constructing electronics to ensure the delivery of appropriate shocks (while avoiding inappropriate ones that could put healthy patients into ventricular fibrillation), and assembling a generator powerful enough to deliver multiple shocks for each fibrillation episode. The pair worked alone, like Greatbatch, and like Greatbatch they used their own money to pay for experimental animals and electrical components. At one point, they stole spoons from a nearby restaurant to make the implantable electrodes. Mirowski had great focus and will. His “three laws” were these: Don’t give up. Don’t give in. And beat the bastards.
In August 1969, Mirowski and Mower put a metal catheter inside a dog’s superior vena cava and a metal plate—a broken defibrillator paddle—under the skin of its chest. With weak current, they induced ventricular fibrillation by stimulating the heart during the vulnerable period. Then, with a single, much stronger twenty-joule shock, they terminated the fibrillation and brought the dog back to life. To publicize their achievement, they made a movie showing a dog first collapsing unconscious in cardiac arrest, then getting shocked by an implantable defibrillator, and finally standing up and wagging its tail. When observers suggested the dog had been trained to fall down and stand up, Mirowski filmed ad
ditional sequences with simultaneous EKG tracings to prove that his dogs’ hearts were indeed fibrillating. The film convinced many doctors that Mirowski was onto something with potentially great clinical benefits. In the spring of 1970, Earl Bakken of Medtronic visited Mirowski to inspect his apparatus. Mirowski performed a successful demonstration for his guest. Afterward, when Bakken asked what would have happened if the revived dog had not been defibrillated, Mirowski disconnected the defibrillator, put the dog back into ventricular fibrillation, and stood by as it quickly died.
A dog collapsing in ventricular fibrillation and then standing up after successful defibrillation (Courtesy of Pacing and Clinical Electrophysiology)
In a monumental blunder, Bakken decided that Mirowski’s device was not commercially viable. Since sudden death is essentially random, he wondered how Mirowski was going to identify patients most at risk. (Mirowski decided to focus on patients who had already survived cardiac arrest. Whether patients with heart disease but no history of cardiac arrest can benefit from an implantable defibrillator is a question that Mirowski was unable to answer and one that cardiologists are still grappling with.) Bakken also wondered how Mirowski was going to test his device. Would he have to put people into cardiac arrest to see if his apparatus worked? (The answer was yes.) Was that even ethical?
So Mirowski and his team continued on their own, undeterred and largely unfunded. On February 4, 1980, they finally did their first human test. The fifty-four-year-old California woman had had multiple episodes of cardiac arrest. In the operation, surgeons at the Johns Hopkins Hospital implanted an electrode in her superior vena cava and sutured a patch electrode to the surface of her left ventricle. They inserted the generator into her abdomen. (As was the case with some medical school cadavers, early pacemaker and defibrillator generators were installed in the abdominal cavity.) Then, to test the device, they put her into ventricular fibrillation. The device did not activate at first. For fifteen seconds, Mirowski and his colleagues watched spellbound as the woman went unconscious. They were getting ready to apply an external defibrillator to her chest when the implantable defibrillator finally fired. One shock was all it took to revive her. Though The New England Journal of Medicine had rejected Mirowski’s first paper on his animal experiments, it quickly published his experience with his first three subjects in a paper called “Termination of Malignant Ventricular Arrhythmias with an Implanted Automatic Defibrillator in Human Beings.” Five years later, in 1985, the Food and Drug Administration approved commercial production of the device.
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Seventeen years after FDA approval, Jack, my patient, was ready to become a reluctant beneficiary of Mirowski’s invention. Lightly sedated with midazolam and Ativan, he lay on a table in the cath lab, his head propped up on a foam wedge to help his breathing. He was relaxed and attentive. When I inserted a needle into his groin in preparation for the catheter, he seemed bemused, even tickled. “Oh my God, look, it’s my blood!” he said.
I had a harder-than-usual time slipping the catheter into the right coronary artery. It turned out to be anomalous, originating from an unusual place. So Dr. Fuchs took over with a differently shaped catheter. “That’s the way it is with me,” Jack said, when I explained to him what was going on. “I’m an anomaly.” Fortunately, the right coronary was clean. The left coronary, too, was mostly normal. There was small plaque in the midportion, but it was unlikely to cause any trouble, so we decided to leave it alone. When I told Jack that we were done with the angiogram, he told us to keep on working. “You can go on for another hour if you want.” The scrub nurse laughed. Jack rather enjoyed being the center of attention. He seemed to appreciate an opportunity to be charming, even if it was on a surgical table.
We transferred Jack to a stretcher and rolled him over to the neighboring electrophysiology suite, where the beeper-sized defibrillator was going to be implanted. Under the intense ceiling lights, his hospital gown was removed. I started off by cleaning his chest with three different antiseptic soaps. Then I pressed a clear antibiotic-impregnated film onto his skin. Defibrillator infections are rare, less than one in a thousand, but when they occur, the device must be surgically removed, so we had to be extremely careful to keep the operating field germ-free. Before long, Jack was getting a milky-white anesthetic, enough so he wouldn’t experience pain during the procedure but not so much that he could not breathe on his own.
Shapiro, the colorful electrophysiology attending, entered with flair. “Honey, I’m home,” he boomed to the nurses. Together, we gowned, masked, and gloved. Then I tipped the table downward to put Jack’s head below his legs so blood would fill his chest veins to make them more visible. Shapiro injected Novocain into the skin and soft tissue. “That hurt,” Jack mumbled, and Shapiro told him to stop talking. “It’s dangerous for you,” he said, winking at me before increasing the rate of the anesthetic drip.
With an electrical knife, Shapiro made a two-inch incision on the left upper chest, close to the shoulder. He dissected through the layer of yellow fat with the blunt end of a pair of scissors, down to the glistening white fascial plane and then below the pectoral muscle, where he burrowed a pocket for the defibrillator. Because Jack was so thin, we wanted to put the device below the muscle so it wouldn’t create too much of a bulge. I stood to one side, mostly watching. Occasionally, I was asked to cauterize a tiny bleeder, and so I’d pull out the electrical knife, releasing a thin wisp of blood smoke. Every few minutes, Shapiro would step back from the table and dance wildly to the song (“Roxanne,” “Rock Lobster”) on the radio.
Before long, Shapiro inserted a twenty-two-gauge needle into a chest vein, pulling back on the hub of the syringe until it suddenly gave way, filling the clear plastic column with maroon blood, a sign of low oxygen tension. He threaded a slippery guide wire, like a guitar string, through the bore of the needle and into the vein. When he knew it was safely in, he pulled out the needle. “Never let go of the wire,” he said, and I nodded nervously. Shapiro threaded a plastic catheter over the wire and pulled the wire out of the vessel, leaving the catheter in place. Then he inserted a thin electrode through the hollow catheter and inched it forward into the heart. On the X-ray screen, it curved into the organ like a snake ready to strike. It buckled ever so slightly when it made contact with the inner surface of the right ventricle. Out came the catheter, leaving the electrode in place. Shapiro then placed a second wire through a large vein and onto the surface of the left ventricle. He slipped the generator, the size of a credit card but about a centimeter thick, into the pectoral pocket and connected it to the wires.
We were done. All that effort over the past several months, and Jack, my magnetic patient, had finally gotten his defibrillator. It was time to test the device by fibrillating Jack’s heart. The Medtronic rep, a courtly, graying man who was there to help with the testing, called for me from across the room. “Step right up,” he said, standing in front of a small computer. “Now you’re going to kill your patient.”
I was supposed to deliver stimuli to the heart during the vulnerable period to induce ventricular fibrillation. I pressed a few buttons on the keyboard to pace the heart three times and then deliver an extra impulse at a variable delay, trying to time the extra impulse into the vulnerable period to cause cardiac arrest. The stream of electrical pulses made cartoonish sounds, like Pac-Man gobbling dots. I started with an extra stimulus at 330 milliseconds. A few squiggles appeared on the screen, denoting a burst of disordered electrical activity, but the rhythm returned to normal. I repeated the test at 320, 310, and 300 milliseconds, with a similar result. But the next beat, at 290 milliseconds, did what we wanted. On the monitor, Jack’s picket-fence heartbeat transformed into a sine wave oscillating at several different frequencies. It was ventricular fibrillation, the rhythm of death. “Here we go,” the rep said excitedly. He started counting: “Five … ten … fifteen.” The defibrillator was programmed to shock after eighteen cycles of the sine wave. Though Jack had been awake
this whole time, when I looked over he was now unconscious. I heard a dull thump, as if someone had driven a fist into Jack’s bony chest, and his body jumped ever so slightly off the table. The defibrillator had fired. On the screen, there was a spike and a pause, and then the EKG returned to normal. A nurse lightly slapped Jack’s face. “Wake up,” she said. “It’s all over.”
Afterward, I asked Shapiro what we would have done if the implantable defibrillator hadn’t worked and external defibrillation was also ineffective. “It’s happened before,” he said. “You get these floppy hearts, and you induce fibrillation, and you can’t always shock them out of it.” He paused and started wiping down his hands. “It doesn’t make us happy,” he said, as if recalling a bad memory. He glanced at me once more. “It doesn’t make us happy.”
Heart--A History Page 16
