Eugene Braunwald is Mega Cardiologist

Braunwald is now and has been for a long time–a Cardiologist of great reputation. He is the long time lead editor of the bible of Cardiology.

Here in a speech given to an international conference, he discusses the important developments and developers of cardiology. In Cardiology Braunwald oughta know.
I just pasted segments of his speech below, highlights if you will.
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The Ten Advances That Defined Modern Cardiology
Eugene Braunwald MD
Full Transcript
Introduction
I think everybody here has their old favorites, and there’s no patent on this, and I think that you can certainly come up with suggestions and have your own group. I’ll tell you about mine.
But, before starting, a few words about the creator of our understanding and the concept of the circulation, William Harvey. Of course, all of us in the room know that William Harvey “discovered” the circulation; but, he did much more. He was the first scientist in biology or medicine, insofar as history records it, who did hypothesis-based experiments. Everything before Harvey, and a lot afterwards, was simple observation. Make observations and atomic observations, pathologic observations, clinical observations. Harvey wondered where the blood came from, and he did two very simple experiments. His hypothesis is, yes, it goes round and round. So, the first thing that he did is he cut the carotid artery of rabbits, and he allowed them to exsanguinate into a beaker, and he measured the volume that was in the beaker, and he found that it was much, much more than the blood that could be accommodated in the arterial tree.
So where did it come from? It must have come from other places. Then he did a second experiment, which he did on himself. He put a tourniquet on his upper arm, found that the veins became congested, took the tourniquet off. The veins collapsed. Okay. Where is that blood going? It’s going centrally. With these two simple experiments—hypothesis-driven experiments—he discovered the circulation and really introduced hypothesis thinking into medical research. And this was his statement. He wrote this famous book, De Motu Cordis, the movement of the heart. It must then be concluded that the blood in the animal body moves around in a circle continuously and that the action or function of the heart is to accomplish this by pumping. That’s it. That’s it. The greatest discovery of all. Okay.
Part 1: Electrocardiography
And cardiology started with Willem Einthoven, who was a professor of physiology in Leiden, and, as we know, he was the father of electrocardiography. There was knowledge among physiologists before that that there were some electrical changes that occurred during contraction and relaxation, but they were measured with something called a capillary electrometer; and that couldn’t be repeated. This is his paper. He used a galvanometer, and you can see the paper is actually in English, and it was published in the Pflügers Archive of physiology. Here is the first ECG machine—pretty amazing, considering what we have now.
This subject’s left foot and his left hand were inserted in brine, which is highly concentrated saline, and you can see the size of the machine. But, the amazing thing is this is the first human ECG. I find it extraordinary because he had conceived of the idea of having heavy lines every fifth of a second and dividing those further. And, of course, Einthoven was rewarded with a Nobel Prize, and he really is the father of modern cardiology, because, what happened after 1903, the first clinical application of electrocardiography was in arrhythmics. This was before Herrick and myocardial infarction, before bundle branch block, before ventricular hypertrophy—it was arrhythmia. And the reason it defined electrocardiology was a doctor who could record this, these squiggles; or who could interpret these squiggles, was a heart specialist. And that’s how cardiology began. It really began with Einthoven.
So, now I want to move from Holland to Saint Petersburg. It became Leningrad and now it’s Saint Petersburg again. Who knows what it will be, maybe Putinburg. But Nikolai Anichkov was the chief physician to the Soviet army; but this is a picture of him close to retirement; he was in his sixties. When he was a young assistant professor in Saint Petersburg, he worked with a medical student, Chalatov. And they did an extraordinary experiment. He had the idea that there might be cholesterol in plaques.
And that started the whole search of atherosclerosis, atherothrombosis, and, obviously, we’re living that today. And this was done by a young assistant professor working with a medical student. My guess is we never heard about Chalatov again, but my guess is he probably did all the experiments.
Well, what has that led to? It has led to what I call the statin pyramid, and I think you are all acquainted with that. What we show in this pyramid is the most extreme, risky population at the top, and the 4S trial with simvastatin, a landmark trial, and then you see other trials below it, and then, at the bottom, you see primary prevention. Now, I think primary prevention and secondary prevention—I don’t know how to separate them. I say “we,” Frank Sacks and Marc Pfeffer led it, and the trial, as you can see at the right-hand side, showed a 24% reduction of death for MI, positive trial of 4150 patients. So, it meant that patients with an average cholesterol also benefited. These were MI patients; so, they would clearly be treated now using the new guidelines.
But look at those two curves; they’re superimposed. And if the trail had been stopped at 2 years, or if the sponsor of the trial said, “You should do an analysis at 2 years—a futility analysis—and if you don’t begin to see a trend, stop the trial.” Well, look at what happened. So, it is almost as if you threw a switch. We have a process in atherosclerosis, which develops, not over weeks, months, or years, but over decades. And I think even powerful drugs won’t turn that around in a couple of months. It took 2 years. Here’s the JUPITER trial, which extended this whole concept to subjects who had only had an average LDL but had an elevated C-reactive protein, and I think you’re all familiar with Paul Richter’s study showing a 44% reduction in patients who were perfectly well, clinically. Okay.
Part 2: Cardiac catheterization
Let’s move on to something else—cardiac catheterization. Werner Forssmann in 1929. In 1929 Werner Forssmann was a 24-year-old resident in urology. And he had the hare-brained scheme that sometimes you want to inject drugs into the heart, but how do you do that? You move a catheter into the heart. See the connection? Catheter and urology? So, he was dealing with catheters all day, every day. But what he did is he went back to the clinic one evening without anybody’s permission; got a nurse to help him. He cut down his own basilic vein, inserted the catheter. He measured out the distance that he thought would take the tip to the right atrium, walked up the flight of stairs and had an x-ray technician take a film. There it is. The first cardiac catheterization in 1939—Werner Forssmann. The next day, his chief came in and he saw what he had done and he was beside himself with fury. He said, “You’re crazy. You do this again, you’re out of here. Never do this again.”
And Forssmann never did it again; but, he did a smart thing. He wrote a paper; one very simple paper, a single case, and, ultimately, that earned him the Nobel Prize together with the other two gentlemen I showed you.
André Cournand was a French physiologist who had immigrated to the United States between the two world wars, and he was a pulmonary physiologist who worked on the Columbia service at Bellevue Hospital in New York. And he systematically began to catheterize the right side of the heart. Now, he did it for a reason we wouldn’t think about very much today. He wanted mixed venous blood; he was a pulmonary physiologist, remember. He was a pulmonary physiologist; he wanted to know how much blood is flowing through the lungs, and for that he needed mixed venous blood, and that’s why he did this.
Now, he was in a very good environment, very different from Werner Forssmann, who was in a small town in Germany. He was at Bellevue Hospital, and he was at Columbia University. People said, “This is incredible.” Particularly, Dickinson Richards, who was his chief, said, “My goodness. We’ve got to do some more of this”; and they did. And they really wrote the book on hemodynamics, congenital heart disease, valvular heart disease, which was very big in the 1950s and 1960s, and cardiomyopathy—the whole works. And I was fortunate enough to be a post-doctoral fellow in that laboratory the year before they won the Nobel Prize. So, they got the Nobel Prize for the three of them—Forssmann, Cournand, and Richards. I moved to the NIH in 1955, after my post-doc with Cournand, and we became very interested in getting into the left side of the heart.
Remember, Cournand was catheterizing the right side. And John Ross, who was a close colleague working in the same catheterization laboratory, developed transseptal left heart catheterization, and we did hundreds of them on patients. So, anybody who would have a right-heart cath also would have a puncture of the interatrial septum and then advancing a catheter over the needle into the left atrium and on to the left ventricle. And this gave us the opportunity, not only to study the hemodynamics of patients with valvular heart disease, but also to do some pharmacologic studies because this was a relatively painless procedure. The catheter was in the left ventricle, and we were able to study both physiology and pharmacology. Now transseptal left-heart catheterization sort of died out.
It died out because the Seldinger technique of doing retrograde arterial catheterization, that was a simpler way to get into the left ventricle in a retrograde fashion.
Part 3: Cardiovascular surgery
Cardiac surgery. My two heroes in cardiac surgery are Robert Gross and John Gibbon. Robert Gross was a professor of surgery at Harvard Medical School. He was the chief surgeon at Children’s Hospital, and he did the first cardiac operation. To be precise, I should say cardiovascular operation, because the first procedure that he did was to ligate a patent ductus arteriosus. It had never been done before, and here is the case report published in JAMA 1939—single case, similar to the first catheterization. So, what did they measure? So, on the x-axis is the day of hospitalization. See the patient was brought into the hospital 9 days before the procedure. That wouldn’t be possible now; you’re lucky if you can get 9 hours before the procedure. And the day of the procedure is shown by the red arrow, and you can see the patient must have had a huge ductus because the blood pressure was running about 120/40 and the diastolic pressure came right up.
So, this was a cure of a cardiac lesion by surgery. Not strictly heart surgery, but close-to-the heart surgery. And the other thing that Robert Gross did is he was the first also to treat coarctation of the aorta successfully and other things like that.
John Gibbon was a professor of surgery at Thomas Jefferson Medical School in Philadelphia, and he had the idea of developing a technique for open-heart surgery, and he was one of these inventors who worked in his garage and developed a heart–lung machine. And he had to develop an oxygenator, and, interestingly enough, he developed a membrane oxygenator, not the kind that was used, and now it’s the kind that has been reintroduced. He successfully treated a 23-year-old girl with an atrial septal defect, and open heart surgery was off and running, and the world would never be the same again.
I joke about cardiac surgery by saying, “All of us are either pre-op or post-op,” and I’m still pre-op, but we’re counting days.
So, there’s another interesting aspect of Gibbon’s pioneering work. He had a friend who was a senior executive, a senior vice president at AT&T, and, when his friend saw what he was doing in the basement, he managed to have some support from AT&T for the development of the first heart–lung machine. And that is an example of an academic–industrial collaboration. I don’t think that John Gibbon profited from that, except it made him a folk hero by developing this machine, and it’s obviously helped millions of patients.
Part 4: Coronary angiography
And then here we are. This is the other side of the coin. That was the surgery; this is not surgery. Mason Sones, coronary arteriography. Mason was the head of the cardiac cath lab at the Cleveland Clinic and very active in the cath lab himself, and one day he did an aortic root injection in the patient to study the ascending aorta.
He thought the patient might have an aneurysm of the ascending aorta. The catheter slipped into the orifice of the right coronary artery; so, the entire injection—the 60 milliliters of contrast—went into the right coronary artery, which as you know, perfuses the sinoatrial node, and two things happen. The patient’s heart stopped. That was the first thing. The second thing that happened was Mason Sones’s heart stopped. And Mason said, “My God. What have I done? What have I done? I’ve injected it into the coronary artery. This is terrible.” And he was going to begin cardiac massage when all of a sudden the dye had passed the sinoatrial node and the heart began to beat slowly. Mason’s heart began to beat slowly. And then they had the films, and nobody had ever seen a coronary angiogram like that. Of course, pathologists had, post-mortem. And Mason Sones is no longer living but the story that he told—I heard it several times—was that afternoon he did four more cases, and he was off and running.
Part 5: Invasive cardiology
And of course, Andreas Gruentzig—it took him 2 years to publish. It took a long time, and this is an abstract, published in Circulation. This was an AHA meeting, and it ended with a very modest conclusion, “The ultimate usefulness of the method remains to be defined”; so, he did not stand up there and thump his chest and say, “I’ve changed the world,” even though he did. And Gruentzig of course, this was his first paper, and this was the first patient who received PTCA. And Gruentzig was a cardiologist, he was a radiologist, and so he had dual training, and I think that was very important. And you can see the arrow on the x-ray on the angiogram on your left pointing to a markedly stenotic right coronary artery, and it looks reasonably good after he dilated it. So, I don’t need to say how important this has been.
Part 6: The coronary care unit
Desmond Julian—interesting story—1961. Desmond Julian was a registrar in the Royal Infirmary in Edinburgh. A registrar is a fellow. It’s beyond resident, but it’s certainly below staff. And he wrote a paper that was published in Lancet on the coronary care unit. So here’s the paper, single-authored paper:
“Many cases of cardiac arrest associated with acute myocardial ischaemia could be treated successfully if all medical, nursing and auxiliary staff were trained in closed-chest cardiac massage and if the cardiac rhythm of patients with acute myocardial infarction were monitored by an electrocardiogram linked to an alarm system.”
And the patients who had MI were usually tucked away pretty far from the nurse’s desk. The reason being an MI was considered to be a wound of the heart, and it has to heal and you don’t want to get patients—wake them up at night with the phones ringing and people rushing around; so, you put them away, often inside rooms, and, in the morning, usually in a large ward of 40 or 50 patients, I’d find 1 or 2 people who had died quietly during the night.
And so the concept of putting them all together really amounted to four things:
First, a technical advance—continuous ECG monitoring with alarms,
Closed-chest CPR—developed at Johns Hopkins. James Jude, a young surgeon, and William Kuowenhoven, who was a retired professor of electrical engineering; one developed the mechanical massage and the other one developed the external defibrillator.
Clustering of MI patients and the empowerment of nurses—that was a social change.She goes and calls the doctor and the doctor hurries over. It takes him only 15 minutes, and that was that. And then somebody had the idea, “Well, my goodness. It’s a nurse and it’s a woman. Could they possibly press the button on the paddle and shock the patient?” And, obviously, you could. And that is what the breakthrough was.
So, these are four advances that have nothing to do with each other. And what Desmond Julian did is he put them together. He didn’t invent anything, but he put it together and I’ve got to tell you—my own memory in 1961—this spread like wildfire across the world. In the United States, by 1964, a general hospital could not get accreditation if it didn’t have a CCU. That’s incredible! Nothing like that has happened before. What happened, the mortality of acute MI in the hospital fell from 30% to 15%. I think Julian should get a Nobel Prize. Okay.
Part 7: Cardiovascular drugs
Cardiovascular drivers—let’s move along. Beta blockers, Sir James Black; ACE inhibitors and statins.
Now, I want to come back to the fact that these are three huge, huge impacts on cardiovascular practice. I would they’re the huge impact on medical practice. Beta blockers, ACE inhibitors, and statins. I can’t even imagine how many hundreds of millions of people have had their useful lives extended. You’ve got to remember, all three of them were done in industrial laboratories. They did not come out of the halls of academia. They came from industry, and we need to be sure that we don’t screw up this academic–industrial relationship. There is so much discussion about it now, and I don’t think people remember this.
Part 8: Preventive cardiology
Preventive cardiology—I’m coming close to the end. Preventive cardiology—now the concept of cardiologists throughout, oh, I guess, until the early ‘50s was that you take care of sick people. And Paul Dudley White, I would consider to be the father of American cardiology; an extraordinary man; very, very modest; enormously influential in a positive way; chief of cardiology at Mass General. In his classic textbook, he began to talk about preventing heart disease and people thought that, “Well, you know, he’s getting old. What is this prevention?” And when I say he was influential, he was influential in starting the National Heart Institute, now Heart, Lung, and Blood, because he was connected at the presidential level; certainly was Eisenhower’s doctor. Now, among the many brainstorms that he had was Framingham—the Framingham Heart Study. And so the concept of prevention and following populations for long periods was never thought about until White, and Kannel was a research fellow.
And I think this paper, published in the Annals of Internal Medicine in 1961, really is one of the key papers by a clinical investigator that was published in the twentieth century. This is the first publication that talks about coronary risk factors. So, these are factors of risk in the development of coronary heart disease. What did he say? High blood cholesterol, high blood pressure, diabetes. My God, have we moved far from there? No. So, I think this is one of the great 10 advances.
Part 9: Echocardiography
Then echocardiography—again, coming out of World War II where ultrasound was used to find submarines and where ultrasound was used to find torpedoes. This was done on both sides of the war. And this is an incredible collaboration. The gentleman that you see on the left was an engineer. His name was Hellmuth Hertz—Norwegian—appropriately named Hertz, which obviously is German for heart, and he couldn’t have had a better name. And, on your right, is a senior emeritus professor of cardiology in Oslo, Inge Edler, and you see he’s holding an ultrasound probe.
And I’m not going to show you the next slide because I’ve talked too long and I do want to come to the final.
Part 10: Pacemakers and internal defibrillators
So, you know, I began with electricity. I began with Einthoven, and then I moved to hemodynamics, and, around 1960, subspecialization began in cardiology, and cardiologists were either electricians or plumbers, and since I had my post-doctoral training in a hemodynamic laboratory, I have identified since then with the plumbers. But I want to say the electricians have done a pretty good job, and I show you two extraordinary electricians: Paul Zoll, who, in 1952, had developed an external pacemaker, and he was a professor at Harvard. And it’s interesting, he also wrote a single-authored paper published in The New England Journal, Resuscitation of the Heart by External Electrical Stimulation. I think Dr. Zipes, who’s been interested in the best, maybe takes some lessons from the fact that this was possible.
And then the final person is Michel Mirowski. Again, this brings us back to the Middle East. Michel Mirowski was a young cardiologist in Tel Aviv who was making rounds with his professor, and his professor had a sudden death. And he was very close, and Michel Mirowski, as he told the story, said that moment changed his life. He wanted to do something about sudden death. And he tried to get it done in Israel, and he couldn’t. And because he was focused on this, he came to the United States. He ended up at Sinai Hospital in Baltimore, and he also was one of these people who worked—he didn’t have a garage, so he worked in his basement—and he came up with an ICD. And then he went a couple miles north to Johns Hopkins, where he developed a very good relationship with the Hopkins cardiologists. Myron Weisfeldt was chief of cardiology there at the time, and Mike made this happen. And, so, in 1980, this is the first clinical paper of the termination of ventricular arrhythmias with an ICD.
The take-home message
So, why is all of this important in terms of human health? Obviously, to us as cardiologists, these are historic moments and you can make up your own list of what you want; I gave you mine. Claude Lenfant gave a lecture in 2003, and he said over 3 decades in the United States—1970 to 2000—there was an average of 6-year extension of the lifespan in America. And, in attributing this, 4 years of those 6 years—so two-thirds of the advances that were made—were made in cardiovascular disease. And you see stroke in there, other heart diseases, 4 years. Perinatal diseases, good; 1 year. Injuries, 1 year. Cancer, a couple of months. COPD, minus; got worse…shortened life. That time, of course, AIDS shortened life much more than it does now. And all other causes, improvements, than a year. So, this is historic. I think that this period will go down in world history; 300 or 400 or 500 years from now is when cardiovascular disease—these were the most extraordinary advances.
Now, not everybody has taken advantage of them, and that’s one thing that we now really need to do, is we have to be able to be sure that everybody in the world has access to these advances.
So, what are the lessons? What are my take-home messages?
Well, with the exception of the first cardiac catheterization and the first coronary angio, there were decades of research by basic scientists and engineers that preceded these advances. So, what I’ve shown you are the tips of the iceberg and what you don’t see, and what we sometimes don’t appreciate, is how many years of work—in other words the ice below the surface—how many years people have worked on, for example, electrophysiology before an ECG could be obtained?
Secondly, the importance of interdisciplinary and academic–industrial collaborations. My goodness, look at echocardiography—a physicist and a cardiologist.
The modesty of the authors. No great claims; certainly did not make great claims, whether it was cardiac catheterization, whether it was the discovery of cholesterol and atherosclerosis, whether it was the development of coronary angiography.
And that these are international efforts, and that’s what we’re celebrating—international effort. This is not made in America. This is made all over the world. The pictures that I showed you of these people come from 11 countries and 3 continents.
So, I think that’s the take-home message. Well, thank you for inviting me to do this lecture.
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