Heart
Page 18
Though patients with heart failure are often literally drowning in their own fluids, their kidneys continue to limit water excretion, incorrectly perceiving a low blood volume because of inadequate blood flow. Treating congestive heart failure is a Sisyphean struggle. The more fluid that is removed with diuretic drugs, the more fluid-retaining hormones get activated. In the end, the therapy becomes its own enemy. Half of all patients with heart failure die within five years of receiving the diagnosis. For the most severe cases, like Ravindra’s, the average survival is only a few months.
The definitive treatment for end-stage heart failure is a heart transplant. The field has progressed quickly over the past several decades. Today the survival rate after cardiac transplantation is about 85 percent at one year, nearly four times better than the average survival of patients treated with medications alone.
But as recently as the early 1960s, heart transplantation seemed like a pipe dream. Organ rejection and life-threatening infections posed prohibitive risks. By the second half of the decade, however, animal research had pointed a path toward human transplantation.
In the end, the race to transplant the first human heart was primarily between Dr. Christiaan Barnard at Groote Schuur Hospital in Cape Town, South Africa, and Dr. Norman Shumway at Stanford. The two surgeons had been residents under Walt Lillehei at the University of Minnesota. By many accounts, they’d had a frosty relationship. Shumway scorned Barnard’s showmanship, his aggressiveness, his willingness to cut corners. Barnard, for his part, resented the way his Minnesota colleague viewed him as a foreigner born into poverty in a pariah country. However, they did share the inspiration of their great surgical mentors, who guided them throughout their careers. It was Owen Wangensteen, the surgical chief at Minnesota, who arranged for Barnard to get his first heart-lung machine at Cape Town in 1958. Before Barnard used it—in the first open-heart surgery in apartheid-era South Africa—he received a letter of encouragement from Lillehei. “Nice and simple,” Lillehei advised his protégé, describing the kind of surgery Barnard should attempt first. “Nothing too fussy, nothing too flashy. I have every confidence in you.”
Barnard was up against a great challenge. In the 1960s, the United States—Stanford in particular—was the mecca of transplant cardiology. Plus, Shumway had a great deal more experience with animal transplants, which he had helped pioneer. In 1959, he and Richard Lower, a Stanford resident, performed the first dog heart transplant. The recipient lived for eight days, demonstrating that an organ could be transplanted from one animal to another and continue to function. By 1967, about two-thirds of Dr. Shumway’s research dogs were able to live for a year or more. In late 1967, he announced in an interview in The Journal of the American Medical Association that he was going to start a clinical trial at Stanford to perform the first heart transplant in a human. “Although animal work should and will continue,” he said, “we are none the less at the threshold of clinical application.” At that point, he had transplanted hearts into nearly three hundred dogs. Barnard had done about fifty.
But Shumway was at a disadvantage when it came to finding a human donor. American regulations at the time prohibited organ harvesting from brain-dead patients if their hearts were still beating. The heart had to stop completely before organs—including the heart—could be collected.* Barnard, on the other hand, was governed by more liberal South African laws—legislation that he himself had presciently advocated for—that allowed a neurosurgeon to confirm death if a patient showed no response to light or pain, a much lower bar than the one for his American counterpart.† By South African standards, once family consent was obtained, a transplant team could quickly harvest organs, including the heart, while they were still being perfused with blood.
It was a close race, but Barnard broke the transplant tape first, on December 3, 1967, thirty-four days before Shumway. His first patient, Louis Washkansky, a fifty-five-year-old grocer, received the heart of a young woman who had suffered brain damage after being hit by a car while crossing the road. He lived for eighteen days after the procedure, succumbing to a lung infection after his immune system was weakened by drugs to prevent organ rejection. Shumway had to content himself with doing the first adult heart transplant in the United States a month later, on January 6, 1968. His patient, a fifty-four-year-old steelworker, lived for two weeks before surrendering to what Shumway described as “a fantastic galaxy of complications,” including gastrointestinal bleeding and sepsis.
Today, with the development of antirejection drugs, the long-term outcomes following heart transplantation are excellent. The median survival is probably greater than twelve years (fourteen, if the patient survives the first year). The success has been a mixed bag, however. Though many lives have been saved, many more have been lost while patients have waited for a viable organ. Only about 3,000 Americans receive a heart transplant each year, though roughly 4,000 are on the transplant list and perhaps ten times that number would benefit from a transplant if an organ were available. Despite public campaigns to increase organ-donor awareness, the number of available organs has remained relatively constant over the years (in part because of seat belt and motorcycle helmet laws that have resulted in fewer road fatalities). For this reason, heart transplants will never be the answer for the 250,000 or so patients in the United States with advanced heart failure. As the Vanderbilt University cardiologist Lynne Warner Stevenson put it, “Relying on transplants to cure heart failure is a bit like relying on the lottery to cure poverty.”
Therefore, replacing the human heart with an off-the-shelf mechanical device has been the great ambition of cardiologists and cardiac surgeons for the past half century. At first glance, the obstacles seem insurmountable. Blood quickly coagulates when it encounters plastic or metal. Without adequate blood thinning, clots can be expelled from an artificial heart and course through the body, blocking arteries and causing strokes and other damage. An artificial heart also can never stop pumping, even temporarily, so without an internal battery to drive the device, power lines must travel into the body, posing the risk of infection. Moreover, even as recently as the late 1960s, a mechanical device had never been housed inside a human body in direct contact with the bloodstream. It was impossible to predict the consequences. And so, even a generation ago, building an artificial heart appeared preposterously wishful. But that didn’t stop some from trying.
Willem Kolff, a Dutch physician, would be the first to succeed. The inventor of the artificial kidney, he moved on to a more vital organ when he performed the first artificial-heart replacement in an animal at the Cleveland Clinic in 1957. Kolff’s organ held two balloon-like sacs filled with blood inside its plastic ventricles. Pressurized air filled the ventricles and compressed the balloons, thus forcing blood out in much the same way as from a beating heart. Kolff’s subject, a dog, survived for approximately ninety minutes. A few years later, at a congressional hearing in 1963, Michael DeBakey, a distinguished surgeon at Baylor College of Medicine in Houston, called for federal investment to support research like Kolff’s. “It is possible to completely replace the heart with an artificial [device], and animals have been known to survive as long as thirty-six hours,” he told the legislators. This idea could reach “full fruition,” he predicted, if there was funding to support more research, especially in bioengineering. DeBakey’s appeal fell on receptive ears. American cardiovascular research had produced a steady stream of life-prolonging innovations over the previous decade, including the heart-lung machine, implantable pacemakers, and external and implantable defibrillators. Despite this progress, heart disease remained the number one killer in the country. Critics, such as Congressman John Fogarty, chairman of the House Appropriations Health Subcommittee—and a cardiac patient himself; he died of a heart attack in 1967—noted that millions were being spent to put a man on the moon. Why couldn’t more money be invested to help Americans dying at home?
And so, in 1964, the National Institutes of Health started the Artificial Hea
rt Program “with a sense of urgency,” as an ad hoc committee advised, with the goal of putting a man-made heart into a human by the end of the decade.
On April 4, 1969, just before the decade ran out, the surgeon Denton Cooley, DeBakey’s great rival at St. Luke’s Episcopal Hospital in Houston, implanted the first artificial heart, made of polyester and plastic and powered by compressed air, into Haskell Karp, a forty-seven-year-old Illinois man suffering from end-stage heart failure. After the implant, which was supposed to provide only a few days of support, a frantic search for a donor heart commenced. A compatible organ was identified three days later in Boston. The donor was put on a chartered Learjet outfitted with a full medical team from Houston, but on the flight home the plane’s hydraulic system failed, and the pilot was forced to make an emergency landing. Another jet was dispatched, but by the time the donor arrived in Houston, they had a problem; his heart was damaged. On the ambulance ride to the hospital, the donor heart fibrillated, requiring electrical shocks and chest compressions to keep it pumping. It was transplanted successfully, but Karp died thirty-two hours after the operation.
Though $40 million of federal money had been spent over almost a decade, many considered Cooley’s attempt premature. More research was needed to design surfaces that would not create blood clots, as well as to develop an internal generator so patients would not have to be hooked up to an external power source. Through the 1970s, many refinements were made to artificial-heart design, including changing the shape of the organ and developing more blood-compatible materials. In 1981, Cooley tried again. This time, the artificial heart provided thirty-nine hours of support, but again the patient died shortly after heart transplantation.
Cooley’s artificial hearts were intended as interim therapy, a temporary bridge to heart transplantation. Neither was designed to be a long-term replacement. However, many patients with end-stage heart failure do not qualify for transplantation because of advanced age or coexisting medical conditions. Such patients require permanent support or “destination therapy,” a bridge not to transplant but to eventual death.
The concept of permanent mechanical support was put to the test a year after Cooley’s second implant when a retired dentist named Barney Clark was wheeled into an operating room at the University of Utah Medical Center. Clark, who was sixty-one, had end-stage heart failure caused by a viral infection. He had originally been scheduled for surgery on the morning of December 2, 1982—coincidentally, almost exactly fifteen years after Christiaan Barnard’s first heart transplant—but when his condition acutely worsened on the night of December 1, in the middle of a heavy snowstorm, his doctors decided to press ahead with the world’s first permanent artificial heart. By the time the seven-hour operation was over, it had unleashed a blizzard of a different kind.
By all accounts, when Clark was hospitalized in late November, he was near the end of his life. For months he had suffered from intolerable shortness of breath, nausea, and fatigue. On Thanksgiving Day, family members had to carry him to the dinner table at his home in Seattle, but he was unable to eat. In the intensive care unit in Salt Lake City, he was placed in a dark room and visitation was restricted; doctors feared that any sort of excitement could precipitate ventricular fibrillation. William DeVries, the lead surgeon, was sure that “death appeared imminent within hours to days.”
Because of his age and severe emphysema, Clark was not eligible for a heart transplant. When his doctors brought up the option of an artificial heart, Clark visited a laboratory at the University of Utah where calves had been kept alive for months with a Jarvik-7 device. The Jarvik-7 was developed in Utah by Robert Jarvik, an engineer working in the laboratory of Willem Kolff, who’d implanted the first artificial heart in a dog at the Cleveland Clinic in 1957 before moving his research enterprise to Salt Lake City. Though the Jarvik-7 carried Jarvik’s name (because Kolff generously named his artificial hearts after the laboratory colleague who had worked on the most recent model), it relied on many of Kolff’s original designs from the 1950s. The aluminum-and-plastic heart had two separate ventricles grafted with polyester sleeves to the native atria and great vessels and was powered by an air compressor that weighed almost four hundred pounds. The sight must have disturbed Clark because he told his doctors that he would take his chances with medical therapy. But worsening heart failure forced him to reconsider, and so in the early morning of December 2, Clark emerged from the operating room with plastic tubes coming out of his chest, connected to a refrigerator-sized machine. Though he was very much alive, his electrocardiogram was a flat line. His own heart had been removed from his body. The Jarvik-7 did its work.
DeVries and his colleagues could not have anticipated the intense worldwide interest in their experiment. Though I was only thirteen at the time, I still remember the daily news coverage. Teams of reporters and television crews swarmed the medical center, hankering for information about Clark’s condition, even sneaking into the intensive care unit to check on him. The hospital cafeteria was transformed into a virtual press club, with hospital spokesmen providing twice-daily briefings. Clark’s private struggle quickly became a public spectacle.
Though he opened his eyes and moved his limbs three hours after the operation, his subsequent course was rocky. On day 3, he underwent exploratory surgery because of air bubbles in his chest wall. On day 6, he suffered generalized seizures that left him in a coma. On day 13, his prosthetic mitral valve malfunctioned, and he had to go back to the operating room to have the left ventricle replaced. Many complications followed, including respiratory failure requiring a tracheostomy, kidney failure, pneumonia, and sepsis. On day 92, DeVries spoke with Clark in a videotaped interview. “It’s been hard, hasn’t it, Barney?” DeVries said. “Yes, it’s been hard,” Clark replied. “But the heart itself is pumping right along.” It continued to pump until he finally succumbed to multi-organ failure on day 112.
Clark’s Jarvik-7 became medicine’s Sputnik; never before had a medical innovation sparked such furious debate, even a kind of national reckoning. Though some doctors viewed the experiment—two decades and $200 million in the making—as successful, most people were deeply disturbed by what they had witnessed. Some were repulsed that the human heart had been replaced by a machine made of metal and plastic. For them, the heart still carried special spiritual and emotional significance that made it impossible to replace with a man-made device. (Una Loy, Clark’s wife, expressed this belief when she worried he might not still be able to love her.) Others felt Clark had not been adequately informed of the hazards of the artificial heart, even though the poor prognosis had been laid out and he had signed two consent forms—eleven pages, doublespaced—twenty-four hours apart to give him time to change his mind. (These concerns seem to ignore the fact that Clark viewed his participation as a sort of humanitarian mission. “It’s been a pleasure to be able to help people,” he said three weeks before he died. “And maybe you folks learned something.”) Still others were troubled by the fact that Clark never left the hospital. He had survived for almost four months, they said. But had he really lived?
After Clark died, there was a period of public disenchantment with artificial organs. The New York Times dubbed artificial-heart research a kind of “Dracula” that was sucking money away from more worthwhile programs. After Clark, three more patients in the United States and one in Sweden were implanted with the Jarvik-7 as a permanent heart replacement. (The longest survivor was a man who lived for 620 days, much of it outside the hospital, but died of strokes and infections.) In 1985, three new artificial-heart models were introduced, including the Jarvik 7–70, which was smaller than its predecessor and powered by fluid, not pressurized air, so large tubes did not emanate from the body. The design, as Jarvik, the engineer, put it, “came from the understanding that people want a normal life and just being alive is not good enough.” However, complications were severe, and most patients died within a few months. By the latter part of the decade, artificial hearts wer
e back to being used almost exclusively as a bridge to heart transplantation. In 1990, the Food and Drug Administration issued a moratorium on the use of the Jarvik-7 device.
Though research began to focus on smaller, novel devices that would assist the native heart, work continued on a total artificial heart. On July 2, 2001, the first fully contained artificial heart with no power lines was implanted in a fifty-eight-year-old man at Jewish Hospital in Louisville, Kentucky. The hydraulically powered device, made of titanium and polyurethane, the stuff of skateboard wheels, was about the size of a grapefruit and had a battery that could be recharged through intact skin, obviating the need for an external power source. The patient lived for five months before dying of a stroke.
Research on artificial hearts continues today. Nearly a hundred patients have been supported with the most recent model, CardioWest. The long-term support record is held by an Italian patient, who survived for 1,373 days before a successful heart transplant. But significant obstacles remain, including infection, bleeding, clotting, and strokes. The most recent devices produce continuous blood flow, so patients emerge from the operating room without a pulse. Continuous-flow devices are simpler than devices that send out pulses of blood, mimicking the native heart. They don’t require valves and have fewer moving parts, resulting in less wear and tear. They still pump blood, of course, but the flow is constant, not periodic. Incredibly, humans, we now know, can live for long periods without pulsatile blood flow. However, continuous-flow hearts produce their own complications. They chew up blood cells because of the shear forces generated by the device and may strip the blood of clotting proteins. For unclear reasons, they cause tiny blood vessels that are prone to rupture to sprout up in the gastrointestinal tract, so patients often bleed internally. They can also cause degeneration in arterial walls and scarring. Continuous blood flow is antithetical to the way that humans, pulsatile beings, evolved. Though continuous flow can keep us alive, it alters our physiology in idiosyncratic and unpredictable ways.