8
Pipes
The tragedies of life are largely arterial.
—Sir William Osler, Diseases of the Circulatory System (1908)
The morning call was from the emergency room. A young man—an intern, in fact, who had been on rounds—had been admitted with chest pains. Could I come to evaluate him?
Such calls about hospital staff were dispensed with some regularity, and they rarely amounted to anything serious. Nevertheless, I hurried downstairs. The ER that morning was its customary mix of drunks and drug addicts. Nurses were just coming in for their day shifts. Stretchers were arranged like latticework in the corridors. There were the usual pressured announcements overhead (“Linda, stat to the trauma bay … Linda”). When I found the intern, Zahid Talwar, he was sitting on the side of a gurney, legs dangling, looking bored. He was about thirty, a Pakistani man with a long face and a long white coat who straightened up respectfully when I arrived. I introduced myself and asked him about the chest pain. It had started after dinner the night before, lasting about ten minutes. He had slept comfortably, but the pain recurred while he was walking to the bus stop that morning, persisting almost an hour. It was a dense pressure in the center of his chest that even he, a psychiatry intern, knew should be checked out. So he had decided to leave rounds and go to the ER.
I wasn’t too concerned. Zahid was young, and his blood tests and electrocardiogram were normal. He had none of the usual Framingham risk factors for heart disease, such as diabetes, hypertension, or a regular smoking habit. I suspected he was suffering from acute pericarditis, a usually benign inflammation of the membrane around the heart often treated with over-the-counter anti-inflammatory drugs. Characteristic of pericarditis, the pain worsened when he took a deep breath. I told Zahid that if blood tests in six hours were normal, we would send him home. I joked there were easier ways to get out of internship duty.
Later that morning, I got a call from an ER physician informing me that Zahid’s pain had resolved completely after he took ibuprofen, further confirming the diagnosis of pericarditis. For a moment I considered sending him home right then, but I decided to wait until the next set of blood tests was complete.
Just before leaving the hospital that evening, I ran into a physician assistant who told me that Zahid’s subsequent blood tests showed abnormal enzyme levels, evidence of minor cardiac muscle damage. This took me by surprise. Pericarditis usually does not result in cardiac damage. I explained that the problem was probably myopericarditis, in which inflammation of the surrounding membrane can partially involve the heart muscle. This, too, was relatively benign. The physician assistant asked me whether the young doctor should have a cardiac catheterization to rule out coronary blockages. I assured him that a thirty-year-old with no coronary risk factors did not have coronary artery disease. I instructed him to draw more blood, and to order an echocardiogram and call me at home if there were problems.
Zahid had chest pains through the night. Doctors who were called to see him attributed them to myopericarditis, the diagnosis written in the chart. At 2:00 a.m., he asked for more ibuprofen. “I told them, if it’s pericarditis, give me more medication,” he told me later. “Means, do whatever it takes to make the pain go away.”
When I saw him in the morning, the pain had subsided. However, further blood tests showed evidence of continuing heart muscle injury, and an EKG now showed new, though nonspecific, abnormalities. Though I still doubted that he had coronary artery disease, I sent him to the cardiac catheterization lab for an angiogram.
I received a call about an hour later asking me to come over to the lab. When I arrived, the angiogram was playing on a computer screen. It showed a complete blockage of the left anterior descending (LAD) artery. The artery looked like a lobster tail, unnaturally terminating after several centimeters. X-rays showed severe dysfunction of the entire anterior portion of Zahid’s left ventricle. My young patient—a doctor—had been having a heart attack for more than twenty-four hours.
•
If, as Osler said, the tragedies of life are mostly arterial, then the source of most of mankind’s misery is the fatty plaque. By cutting off blood flow, obstructive arterial plaque is responsible for heart attacks and strokes, the most common ways we die. By the 1960s, the mechanisms underlying this process were being aggressively investigated. In 1961, the Framingham study confirmed that cholesterol is a risk factor for coronary heart disease, but it did not explain why. In the decade following, scientists showed that when the concentration of blood cholesterol gets too high, small cholesterol particles can burrow through the inner lining of blood vessels and take up residence inside the wall. This begins benign, but the cholesterol soon reacts with oxygen to form free radicals that injure nearby cells. As these injured cells release chemical signals—calls for help—white blood cells swarm to the site of injury. There, they transform into cells called macrophages that feed on the oxidized cholesterol. Bloated by this indigestible cholesterol, the macrophages turn into “foam” cells, padding the vessel’s wall. They continue to gobble up cholesterol until they pass the brink of rupture, vomiting a gooey paste into the wall. The domino effect continues as more macrophages are recruited to the site, multiplying, causing the lesion to enlarge. Scar tissue is deposited to form a crust over what is now a malignant soup of fat, digestive enzymes, swarming macrophages, and dead cells—a full-fledged atherosclerotic plaque. In the beginning, the artery expands to compensate for the intrusion of plaque into the space within, but as the lesion gets bigger, the plaque eventually pushes into the vessel, hindering blood flow.*
The physiology of atherosclerotic plaque was mostly understood by the early 1960s, but how to treat it? As with any pipe, the first step is to pinpoint the blockage, not an easy feat in the dark caverns of the human body. On a temperate October day in 1958 in Cleveland, Ohio—just two years after Werner Forssmann received the Nobel Prize—Mason Sones, director of the cardiac catheterization lab at the Cleveland Clinic, came up with a solution to this problem.
Like Forssmann, Sones was a bit of a lunatic. Even in an era when doctors lived and breathed medicine, Sones topped the charts. He routinely worked until midnight, holding his cigarettes with sterile forceps while he smoked in the cath lab. Then, instead of going home to his wife and children, he’d peel off his stained white undershirt and go out for drinks at a nearby hotel. Nurses and secretaries were known to hide from him in the ladies’ bathroom. He’d soon catch on, pounding on the door whenever he had a task that demanded their immediate attention. Like Forssmann, Sones was brash and bullying. Like his great predecessor, he skipped animal studies and went straight to human demonstration. And like the German, he had the brazenness—and perhaps the good fortune—to go first.
Coronary arteries (Courtesy of Scott Weldon)
The coronary arteries take off from the aorta, the main artery in the body, just beyond the aortic valve. In the 1950s, cardiologists, fearful of putting a catheter directly into the coronaries, would inject massive amounts of dye into the aortic root, hoping some of it would trickle into the coronaries so they could be visualized by X-ray. Such “nonselective” injection was a feint, a sort of foreplay, and it provided few useful images.
One October morning, Sones was getting ready to inject dye into the aortic root of a twenty-six-year-old man to image the vessel in preparation for open-heart surgery when, as he was moving the catheter into position, it slipped into the opening of the right coronary. I learned during my fellowship that because of the shape of the aortic arch, it is almost easier to insert a catheter into the right coronary than to avoid it. Sones knew this, too, and whenever the catheter slipped into the orifice, he would withdraw it a few millimeters to disengage it. However, this time, before he could do anything, his assistant stepped on the dye pedal and dumped 50 cc of dye into the artery.
In a letter to a colleague, Sones recounted the fateful episode:
When the injection began I was horrified to see the right coron
ary artery become heavily opacified and realized that the catheter tip was actually inside the orifice … I ran around the table looking for a scalpel to open [the patient’s] chest in order to defibrillate him by direct application of the paddles … Fortunately he was still conscious and responded to my demand that he cough repeatedly. After three or four explosive coughs his heart began to beat again.
He later wrote,
Initially, I could feel only unbelievable relief and gratitude that we had been fortunate enough to avert a grievous disaster. [But] during the ensuing days I began to think that this accident might point the way for the development of a technique, which was exactly what we had been seeking.
Sones’s technique, called coronary angiography, outlined the flow of blood in the coronaries using dye and X-rays, thus pinpointing the location of plaque. “I knew that night that we finally had a tool that would define the anatomic nature of coronary artery disease,” he said. However, as is often true in medicine, diagnosis was only the first step toward a cure. It took almost two decades after Sones’s breakthrough to develop this “cure.”
In the meantime, scientists focused on perfecting nonsurgical treatments for patients who’d suffered heart attacks. In 1961, Desmond Julian, a cardiology fellow at the Royal Infirmary in Edinburgh, Scotland, published the first paper on the benefits of housing heart attack patients in a special cardiac care unit. “Many cases of cardiac arrest associated with acute myocardial ischemia could be treated successfully if … the cardiac rhythm of patients with acute myocardial infarction were monitored by an electrocardiogram linked to an alarm system,” Julian wrote. Before the advent of such monitoring, most patients who suffered heart attacks were housed for weeks in rooms off the main medical ward, far from ringing phones and the hustle and bustle of the nurses’ station, to give their hearts peace and quiet and a chance to heal. This benign neglect exacted a heavy toll, however. Senior cardiologists from that era have told me that when they would come to the medical wards early in the morning to draw blood, they’d often find one or two cardiac patients who had died quietly during the night.
Like other CCUs, Bellevue’s had a bank of EKG monitors that continuously tracked patients’ heart rhythms. Defibrillators and other resuscitation equipment were on standby. The nurse-to-patient ratio was 1:3 or sometimes even 1:2. Such vigilance saved lives. One morning, soon after my fellowship began, a middle-aged woman in her third day after a heart attack went into ventricular fibrillation, the chaotic rhythm that killed both my grandfathers. She had been feeling well and was eager to go home; her only complaint was of the EKG stickers irritating her skin. Then she slumped over. Her eyes rolled up in her head, and her face turned bluish, like an old bruise. If I had opened her chest at that point and held her fibrillating heart in my hand, it would have felt like a bag of swarming worms. I stepped into the hallway and shouted for an external defibrillator. An attending physician ran in and delivered two hard punches to her chest, “precordial thumps” that can sometimes terminate fibrillation, though that morning they did not. We inserted a board under the patient’s body and started chest compressions. When the defibrillator was brought in, I applied the metal paddles to her bony frame. One 360-joule shock was all it took. She coughed twice, her pulse reappeared, and she took a deep breath. Her eyes opened wide, and she turned her head to face us, looking sheepish, puzzled by all the commotion. She had no idea we had saved her from certain death. Her roommate in fact was more traumatized. Rocking back and forth in her bed, she quietly asked me to draw the curtain closed.
•
So, by the early 1960s, cardiologists could image a coronary obstruction. But how to fix it? Surgeons were already bypassing vascular obstructions in the legs and in the heart using vein grafts harvested from various sites in the body. However, mortality and morbidity rates in these bypass operations were unacceptably high. So a cadre of zealots began to try to figure out ways to create new channels of blood flow, not around a blocked artery but through it.
One of these doctors was Charles Dotter, a radiologist at the University of Oregon. At a conference in Prague in 1963, Dotter predicted that the angiographic catheter could be “more than a tool for diagnostic observation. Used with imagination, it can become an important surgical instrument.” Dotter—“Crazy Charlie,” to some—was an odd bird: a mountain climber, ornithologist, and amphetamine addict. He fashioned guide wires for his procedures out of guitar string, and at conferences he blowtorched catheters out of Teflon tubing at his hotel. Once, in the middle of delivering a lecture on cardiac catheterization, he rolled up his shirtsleeve to reveal to the audience that he had placed a catheter in his own heart that morning. Then, as he continued to lecture, he connected himself to an oscilloscope to record the pressures from his cardiac chambers.
Dotter performed the first therapeutic procedure with a catheter, which he called angioplasty, on January 16, 1964, when an eighty-two-year-old patient named Laura Shaw, who had a blocked artery in her leg that had resulted in gangrene, was brought to his radiology lab. Her limb was crusty, dusky, and infected. Even though she was in terrible pain, she refused amputation. As a palliative measure, Dotter inserted a wire through the skin on the back of her knee and into the blocked artery and then sequentially passed concentrically enlarging plastic catheters over the wire to dilate the vessel, relieving the obstruction by packing the plaque onto the vessel wall “like footprints in the sand.” The procedure was successful. Shaw’s pain subsided, and the infection resolved. She succumbed two years later to a heart attack.
For this and subsequent leg procedures, Dotter received widespread publicity. In August 1964, Life, the most widely circulated periodical in the country, published a photo spread of Dotter posing oddball during one of his clog-clearing procedures. “Things have been both rewarding and at times frustrating,” Dotter told the magazine. “In the early days of … angioplasty I had to accept a lot of unpleasant backbiting, such as ‘He’s a nut, you can’t trust his uncontrolled, poorly documented case experience,’ and worse. I’m glad I was thick-skinned enough to stick with it.”
Angioplasty was simply unclogging a pipe, and in fact Dotter frequently referred to himself as a plumber. “If a plumber can do it to pipes, we can do it to blood vessels,” he said. But his technique was coarse and crude, often resulting in a sort of snowplowing of plaque down the artery, where it could filter into smaller branches, obstructing them. Vessel injury was common, resulting in tears, bleeding, and scarring. Sometimes the plaque would dislodge and travel down the artery, causing infarction and tissue death. Though Dotter suggested that a more controlled dilation would be safer and more effective, he was never able to develop this method.
That critical step was left up to another German physician, Andreas Gruentzig, who began toying with Dotter’s catheters in the late 1960s. Like so many of the great cardiac innovators, Gruentzig was an engineer at heart. His two-bedroom flat in Zurich was across the street from where James Joyce wrote much of Ulysses, and his kitchen table, laid out with drawings, knives, plastic tubing, air compressors, and epoxy glue, was in fact a portrait of an artist’s work space. Gruentzig often worked all night fashioning prototype catheters. When colleagues would visit—at all hours, to the chagrin of Gruentzig’s long-suffering wife—he would lead them to his kitchen and put them to work. With a mane of black hair and a burly mustache, Gruentzig was handsome and charismatic. Like Forssmann, his legendary predecessor, he was a risk taker, winging his single-engine plane low over the Swiss Alps on weekend getaways. But unlike Forssmann, he worked systematically and inspired followers.
Gruentzig set as his task adding an inflatable balloon to the end of his catheters that was thin but strong enough not to compress or burst when encountering arterial walls studded with plaque. He first tested these balloon catheters on anesthetized dogs that he smuggled into the hospital on gurneys under drapes. The dogs’ arteries were stitched half closed to mimic an atherosclerotic blockage. When those experiments prove
d successful, Gruentzig went to work on human cadavers. On February 12, 1974, ten years after Dotter’s first angioplasty, Gruentzig used one of his catheters to perform the first human balloon angioplasty on a sixty-seven-year-old patient with a severe stricture of the iliac artery, a major vessel in the leg. After the balloon was inflated, relieving the blockage, an ultrasound showed free-flowing circulation, and the patient’s incapacitating leg pain vanished. Following this triumph, Gruentzig began to perform balloon angioplasty on a regular basis, handcrafting catheters for every new patient and meticulously tracking his results to deny voice to his critics. It was difficult, painstaking work. “If I had an enemy, I would teach him angioplasty,” he wearily told a colleague.
However, the ultimate goal for Gruentzig and others was the coronary artery, whose disease was responsible for so much death around the world. “The legs were only my testing ground,” Gruentzig said. “From the beginning I had the heart in mind.” Dotter himself wrote that the development of coronary angioplasty was “one of radiology’s most pressing responsibilities.” However, the idea of balloon coronary angioplasty was heretical in the extreme. There were so many potential pitfalls. The balloon could puncture the artery, causing rapid hemorrhage and pericardial tamponade. The vessel could recoil and close, causing a massive heart attack. The heart could develop fibrillation and stop beating altogether. For years, Gruentzig’s ideas were met with disdain, motivated by fear and perhaps not a small amount of jealousy. But he was a man of conviction, and there was nothing Gruentzig believed in more than himself.
Heart Page 13