The Heart Healers (30 page)

I had attended the autopsies of patients who died of acute myocardial infarction, so I knew that a blood clot, called a thrombus, was sometimes found in the coronary artery. We considered it an uncommon incidental finding of no great importance, agreeing with my friend Dr. William C. Roberts, chief of the cardiac pathology at the National Institutes of Health, who said, “Although it may play a major role in causing atherosclerosis, coronary thrombosis may well play a minor role, or none at all, in precipitating a fatal coronary event.” Roberts, like the rest of us, believed that diminished blood flow led to death of the heart muscle, and blood clots then formed in the damaged arteries. As an international lecturer, I had pontificated innumerable times with professorial grandiosity on the imbalance between oxygen supply and demand, not blood clot, as the cause of myocardial infarction. But Roberts and I were wrong.

In his modest way, Marc almost apologetically unveiled his discovery, careful not to insult the ego of one of his mentors. He knew I was wrong, but he would let me discover it for myself. When his surgeons opened the culprit artery to attach a bypass graft, Marc was stunned to find that the vast majority of his still-living patients had a thrombus that completely obstructed their coronary artery. His mentors, among them me, had taught Marc that heart attack was the product of oxygen supply/demand imbalance, and that the thrombus came later. He showed me photo after photo of clots he had fished out of the vessels. There they were: evil, glistening, gelatinous red worms, now lying inert with a ruler lying next to them. They were about a half-inch to an inch long. Marc said nothing, looking at the photographs, as I shuffled through them a second time. As I sat back he raised his eyes and spoke softly.

“In almost every case,” he said.

I am not sure how long it took me to absorb the full import of that sentence. I do know that during our meeting I felt like St. Paul on the road to Damascus … I had just experienced an astounding revelation. All my life, I had been wrong and now I saw the light. Like Paul, I underwent an instant conversion. “Marc,” I finally said, “you have made an incredible discovery … it will completely change the treatment of acute myocardial infarction. You have got to publish this as soon as possible.”

Less than a year later Marc formally announced to the world in
The New England Journal of Medicine
that a heart attack was not caused by our imagined progressive narrowing of a coronary artery. A heart attack was caused by the sudden occlusion of a coronary artery by an unseen blood clot, a coronary thrombus. His manuscript astounded the cardiologic world. It now stands as one of the most widely quoted manuscripts in the vast corpus of clinical cardiology research in all my years of cardiology. He reported that he had found thrombus in the coronary artery of 87% of patients operated on within four hours of the onset of symptoms. In one single powerful stroke Marcus DeWood’s photographs collapsed the venerated citadel of oxygen supply/demand as the cause of heart attacks.

Before we chronicle the impact of Marc DeWood’s revelation, let’s look at it in the broad context of scientific discovery. He had begun with beliefs rooted in the past, yet he had illuminated the future. As Dr. Siddhartha Mukherjee observes of cancer research in
The Emperor of All Maladies,
“Scientists study the past as obsessively as historians because few professions depend so acutely on it. Every experiment is a conversation with a prior experiment.” Like ancient city architects, in medical research we build upon the work of those who came before us. When we do well, we confirm and extend the knowledge that preceded us. When we succeed brilliantly, however, we destroy the existing structure. And thus every great new theory is a refutation of the old. DeWood’s discovery of the unanticipated blood clot demolished conventional wisdom on the cause of heart attack.

DeWood’s revelation left us with a baffling question: How could a generation of pathologists and cardiologists have missed all these clots at autopsy? I had stood at the autopsy table of many heart attack patients as the pathologist opened each coronary artery along its entire length. Like Bill Roberts I was quite sure, certain really, that there were no clots in most of those vessels. The pathologists and I had blundered. How? Put simply, we should never have believed our lyin’ eyes. We assumed that what we saw in death represented what existed during life. We assumed that the autopsy gave us a chance to see in intimate detail what we had been unable to see hours before during life. Our assumption was founded on centuries of experience with every other disease in every other organ. But this time the autopsy was wrong. Dead wrong.

As a blood clot forms, the body’s natural mechanism for dissolving the clot also swings into action. This process, called thrombolysis, can dissolve a small clot in a matter of hours, a large clot in a day or so. This mechanism makes biologic sense. Blood clots form to stop bleeding. But once the bleeding is controlled, we want to restore flow to the tissue beyond the clot. Both thrombosis and thrombolysis are a biologic necessity. In the case of the coronary artery, the sudden appearance of a clot in a coronary artery caused death of heart muscle. But in two-thirds of the cases of death from heart attack, by the time we opened the culprit vessel on the autopsy table the clot, like a snake in the grass, had slithered off after creating its devastation. DeWood sealed his proof that clots in coronary arteries disappear with time by analyzing patients who came in at twelve to twenty-four hours after symptom onset. By that time only 65% had a coronary thrombosis. We had not missed the clots at autopsy; they were not there. The nefarious clot had wreaked its damage and disappeared. As unwitting members of the flat-earth society we assumed that our single snapshot several days after the heart attack represented what existed at its moment of onset. Our logical error recalled my medical school’s yearbook with a photo of a curmudgeonly professor with a humorless grin and the caption, “True, it’s a small point, but you fail.”

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IN THE EARLY
1980s Eduardo Flores, a forty-two-year-old father of two and a chef at a popular Mexican restaurant in Southwest Los Angeles, had just returned to work from a three-day bout with the flu. Perfectly bilingual, Eduardo’s face and brown skin limned his ancestry, more Peruvian Indian than Caucasian. His nose formed a continuous straight line with his forehead; his black hair had flecks of gray. Eduardo had always been a powerful man, with a hairy barrel chest and legs like tree trunks. Entering his fifth decade of life, you could still imagine the physique of the football tackle he had been in high school, although the recent years had not been particularly kind to his waistline.

Eduardo had returned to work with the perpetual good humor and openness that marked his life. Why not? For his first forty-two years he had never been seriously ill. Aside from childhood appendicitis, he had never been hospitalized. It was true he was a smoker since high school, but with a dedicated wife, the constant amusement of a toddling two-year-old son, and another on the way, he had vowed to eliminate cigarettes from his life.

Eduardo’s indigestion began a few minutes past three in the afternoon after he gulped down a quick lunch. Looking back, although the pain was not initially severe, his mind retained the commonplace details at the moment the discomfort first entered his consciousness: baskets of chips on the counter near the kitchen’s swinging door, the dishwasher stacking clean plates, his salad man chopping green peppers. Had his subconscious warned him at that instant that this pain was destined to be different from any other? He recalled wondering idly if a chef should ever admit to indigestion caused by his own menu. He popped a couple of Tums and continued preparing for the dinner crowd. Over each minute of the next half hour, however, the discomfort of indigestion ratcheted up, notch after notch, blossoming first into his chest and into his jaw. By now it dominated his every thought. He told his sous-chef to get help. A few minutes later, he was engulfed with a sudden unshakable feeling of impending doom. Just after 4 p.m. Eduardo Flores stood up from a chair someone had brought in, staggered forward a few steps, and collapsed to the floor. Without prior warning, once powerful Eduardo Flores had been struck down, brought to his knees by a stunningly swift, now excruciatingly painful, terrifying blow to the chest.

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HAD EDUARDO FLORES
collapsed when I entered college, he quite likely would not have survived to reach the hospital. But if he had, he would have been given a stool softener, some pain medication, and put to bed for three weeks with gradual progression from bed to sitting in a chair. Every doctor of that era recalls the great anxiety surrounding that bedside-to-chair moment. He would have had spent another three weeks at home at bed rest. That was all we had to offer.

The cardiology fellow who met Flores in the Emergency Department saw a characteristic change in his ECG. The familiar narrow spike of the normal ECG had become quite wide and almost rectangular. In the macabre humor of medicine, the upright rectangular shape of the ECG is called “the tombstone ECG,” the signature of the highest risk type of myocardial infarction. This ECG pattern indicates a clot obstructing the left anterior descending coronary artery near its origin. Pathologists have called this vessel “the widow maker” with good reason. I had told the staff that I wanted to be notified when we had a patient for a new clot-dissolving treatment for myocardial infarction because I wanted to witness the breakthrough that I thought would revolutionize the management of heart attacks around the world. When the call came, I grabbed my tape recorder and raced up a flight of stairs to observe the treatment in the cath lab to record an oral history of the event.

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MY EAGER ANTICIPATION
was based on a research program in our Specialized Center of Research. DeWood’s discovery created a new direction for therapy. We began the search for an agent that would very rapidly dissolve the clot in the coronary artery. Ironically a potent agent for dissolving blood clots had been identified some forty years earlier. Called streptokinase, it had even been tested in acute myocardial infarction in the late 1950s by Philadelphia hematologist Dr. Sol Sherry. His group reported that when streptokinase was given within four hours of symptom onset, hospital mortality was reduced, whereas if treatment was delayed beyond that time it had no beneficial effect. Yet we cardiologists had ignored Sherry’s report. After all hematologists were members of a different guild, and we were blinded by our belief that coronary thrombus did not cause myocardial infarction.

Even if we could dissolve a clot in a patient’s coronary artery, however, a new question arose. Would restoring blood flow through the obstructed vessel have any benefit? How long did it take heart muscle to die after it was deprived of blood flow? Would our treatment be too late? We had no answers to these simple questions. In San Diego, investigators in Dr. Eugene Braunwald’s laboratory reported that if they released a tie around a coronary artery after half an hour, the heart showed evidence of partial recovery. Meanwhile in our animal laboratory Willie Ganz created a coronary thrombus in an anesthetized dog by inserting a copper coil. The heart muscle beyond the clot turned blue and stopped contracting within five or ten heartbeats.

Willie called me in to see what happened next. He infused streptokinase directly into the obstructed vessel. Standing beside him in the laboratory, I was dumbfounded by what I saw, an event as spectacular as anything I have ever seen in the research lab. Willie’s infusion dissolved the clot, and it did not take long … sometimes it dissolved in as little as ten minutes. As the clot dissolved, I saw the blue noncontracting, apparently dead segment of heart muscle become pink, and it began to contract again. In that moment, I knew that I was a witness to what would become a worldwide breakthrough in the management of acute myocardial infarction.

A footnote to history that still amazes me today is that when Willie and I submitted his preliminary results in a modest grant request to the National Institutes of Health for financial support of what was to become landmark research in cardiology, his request was rejected because his anonymous reviewer turned wine into water, asserting that the clotting system of dogs was not necessarily similar to man. But when innovators battle the establishment, innovators usually win. Seriously miffed, I found other sources to support Willie’s research, and years later I nominated Willie for the American College of Cardiology’s annual Distinguished Scientist Award, which he received at the college’s annual convocation ceremony to a standing ovation from many hundreds of cardiologists. I never learned who had so firmly planted his jackboot on the neck of progress. I only hope that his retribution requires that he pay full price for this book. Meanwhile in Russia, Germany, and our hospital a new cadre of pioneers began their first attempts to infuse streptokinase into the coronary arteries of patients with acute myocardial infarction.

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WHEN OUR CARDIOLOGY
fellow diagnosed acute myocardial infarction in chef Eduardo Flores he immediately activated the signal for a “Code White,” which meant the cath lab was to be readied for immediate infusion of streptokinase directly through a catheter inserted into the coronary artery. When we first began giving streptokinase we feared that the drug might cause irreversible bleeding, perhaps from an unrecognized stomach ulcer or even within normal brain tissue. So to minimize the dose we infused it directly into the culprit coronary vessel, mimicking the way Willie Ganz had dissolved clots in the animal lab.

In treating acute myocardial infarction, you are on the clock. Every action by each team member is done in controlled haste. I watched our cath lab director Dr. Harold Marcus rapidly pass a catheter from the groin into the left coronary artery, then inject contrast material to outline the vessel. As I saw blood enter Eduardo’s left coronary artery, then abruptly stop, my brain flashed momentarily on Marc DeWood’s photo of the evil red worm lying inert on a towel. There it was in life; the clot abruptly cut off blood flow and Eduardo’s heart muscle fibers beyond it were dying. In acute myocardial infarction, time is muscle: the faster the obstruction is cleared, the less heart muscle dies. Now Harold began the intracoronary streptokinase infusion, and we waited for the clot to dissolve. After about half an hour, Eduardo’s ECG began to change. Like a snowman melting, the rectangular “tombstone ECG” began to disappear, returning toward its familiar normal spiked shape. Eduardo also reported that his chest pain was markedly less. These are two cardinal signs of restoration of blood flow in a coronary artery, which we call a “reperfusion.” We knew we were witnessing signs that his artery had reopened.