 Hello, everyone. I'm Bob Trug. I'm the director for the Center for Bioethics at Harvard Medical School. And I'm here today to interview Professor David Jones, the Ackerman Professor of the Culture of Medicine here at Harvard Medical School, about his recent book, Broken Hearts, The Tangled History of Cardiac Care, published by Johns Hopkins University Press in 2014. David, welcome, and thank you for being here to talk about your book. As you point out, cardiac disease is the leading cause of death worldwide. And the last several decades have seen the development of many new ways of treating this disease. And literally, patients and doctors every single day are having discussions about what this problem is and how to manage it. And your book gives us such an insightful history about how that conversation has developed over the past several decades. No, it's an incredibly interesting problem, because one of the things that you realize as you dig into this history is how hard it was for doctors to understand the nature of what the problem was and how best to respond to it. Even though heart attacks have been the leading cause of death in this country for most of the 20th century, it was really only in the 1970s and the 1980s that doctors developed a good understanding of what the cause was. And without that good understanding of cause, it was very hard for them to figure out how best to treat this disease. Yes, I mean, that was one of the most interesting things to me is that there have been at least a couple of different theories that have been out there that have very much driven the way that doctors thought, how doctors thought this disease should be treated. Could you say a little bit more about that? Yeah, it simplifies the history of it, but there were two basic theories that they came up with. One theory focused on the way that cholesterol plaques would accumulate slowly and gradually over the course of a lifetime. You don't see many of them in a child. You see many of them in a 70 or an 80-year-old. And the idea was, as these accumulated, eventually they cause problems in your coronary arteries. And the goals detect large plaques as soon as you can. And then to do something about them before they actually cause a heart attack. And doctors developed technology that would allow you to do that, a fancy form of x-rays that would allow you to see the plaques. And then these techniques of coronary artery bypass surgery and coronary angioplasty that would allow you to remove, manage, stent, or bypass these plaques before they cause problems. So that was very much a surgical solution. The other theory was that heart attacks were caused by the rupture of a coronary plaque, often a small one, one that you can't see on imaging techniques. And so the typical 50-year-old American might have dozens of these fragile plaques, all of which essentially a time bomb waiting to happen. There's no way to do procedures against 20 or 30 of these plaques. The only way to treat them is to do something that affects all of them, either through changing your lifestyle, quitting smoking, or exercising more, or taking medications. And so these two different theories, progressive obstruction versus plaque rupture, would motivate very different kinds of therapeutic response. Procedures on one hand, or medications, and lifestyle changes on the other. So we get to the point where there's a variety of different treatments for this condition. You have bypass surgery, which can be done on the pump or off the pump. We have interventional cardiologists who are doing angioplasty. And patients and doctors need to decide which of these treatments they're going to have. And I think one of the amazing points you make is that it seemed that the treatment you got was determined more by your zip code than by necessarily what the evidence was for each of these or the types of complications that would be better or worse for any given person. Was that unique to this? Or is that a common problem in medicine today? Well, let me answer that. And then I want to back up a bit to explain another part of this. But the issue of geographic disparities in treatment has become a huge problem in healthcare. Doctors first became aware of this issue in the 1930s. There was an interesting article that was published in London showing that tonsillectomy rates varied enormously across different neighborhoods in London. And there was no rhyme or reason to explain why there was a nearly 30-fold variation in tonsillectomy rates in different neighborhoods within the city of London. That finding didn't get much attention at the time. It really wasn't until the late 1960s when researchers in the United States started to look at this more carefully. In part because they were concerned about the rising costs of healthcare that happened soon after Medicare was passed. And so Congress realized that healthcare costs had risen steeply between 1965 and 1970, and they started funding researchers to look at what doctors were actually doing. And as doctors did this, they realized there was this huge amount of variation and surgery was the easiest thing to study because you can just count how many operations are surgeons doing. And they realized there were huge disparities in surgery rates from one town to another and also not just by geography, but also by race of the patients. In general, in the United States, white patients were getting procedures at higher rates than black patients. And people were concerned about this because they believed that if doctors were really practicing evidence-based medicine, these sorts of variations shouldn't exist. Now, if there was a difference in heart disease prevalence between one state and another, there might be a difference in heart disease procedures between one state and another. But this was never the case. The variations in procedures had nothing to do with variations in the disease itself. And it wasn't just true for heart disease. It was for all areas of surgery and eventually shown for other areas of medical practice as well. So it was a ubiquitous problem. And physicians were very concerned because it suggested that there was something irrational about medical decision-making. Part of the history that you describe is that the expectations of patients may have far exceeded the reality of the benefit of these procedures. Can you say more about that? That's only been a huge problem with these cardiac interventions. And I think it's true throughout medicine. Over the past 20 years, researchers have done surveys of patients and shown that patients often have hugely unrealistic expectations. One survey found that patients expected that having angioplasty would increase their life expectancy by 10 years. Now, for most patients, angioplasty has never been shown to have a survival benefit, let alone increasing life expectancy by 10 years. There are almost no medical procedures that would have such a huge benefit, certainly not angioplasty. The patients often believe that. The question is where is that coming from? Are they being told this by physicians? Are they reading this in newspapers? Or is this somehow result of patients who desperately want to get better, who hear some claims, they misinterpret the claims and develop this exaggerated sense all on their own? It's not clear where it comes from, but it's a huge problem because if you have unrealistic expectations of benefit, you're more likely to intervene, have these procedures, they can be expensive, they can have complications, and then you're not gonna achieve the benefit that you were hoping for. You know, right from the beginning, as you describe, people did recognize that there were some major complications to these procedures, strokes and things like that. But we now know that perhaps as many as 80% of patients who undergo, say cardiac bypass, end up with these more subtle neurological and psychological symptoms that were not appreciated. Why were people so slow to pick up on those? Well, one of the problems here is that the brain is a complicated organ that does all sorts of things, many of which are quite subtle. And so after patients had surgery, if it was simply a case of surgeons examining their patients to see if anything had gone wrong, surgeons would detect significant strokes, but they often wouldn't detect subtler problems. Researchers began to collaborate with psychiatrists, neurologists, psychologists, and they would do complicated testing on the patients. And if you did that, if you really looked carefully at these patients, you would see far higher complication rates, not just a 3% risk of stroke, but an up to an 80% risk of personality change, cognitive deficits, strange reflexes that were evidence of brain damage. And then the patients faced a difficult choice. Were these findings actually significant? Surgeons would say, well, yes, there are measurable deficits that you can see, but routine life doesn't require the level of cognitive function that neuropsychological testing does. And so, yes, we can detect these problems, but they're not actually significant to patients. Now, I wouldn't be very reassured by that explanation, and I don't know how most patients would be respond to being told there is brain damage, but you won't notice it, so don't worry about it. You know, another theme that struck me as I was reading the book was the way that the clinicians and researchers involved were really focused on what the benefits of these procedures would be, and we're largely blind to potential complications, particularly related to the brain and psychiatric phenomena. And this is something that you certainly see in cardiology and cardiac surgery, but is by no means limited to those areas of medicine. The challenge here is when you develop a new therapeutic intervention, you know exactly what you want it to do, and it's quite easy to study, or should be easy to study, whether the treatment does what you want it to do, because you know the outcomes that you're looking for. And so, if you have a treatment that your hope will increase blood flow through the coronary arteries, then you study patients afterwards to see if blood flow has indeed increased, and if the flow has increased, then the treatment did what you wanted it to do. The problem is, if you're looking for complications, you might not know in advance what complications the treatment could cause. And so, you have to pass the very wide net and do all sorts of studies to figure out all the things that could possibly go wrong. And this is very difficult research to do. Now, in the case of cardiac surgery, when cardiac surgeons started performing cardiac surgery in the 1950s, they developed this new technology, heart lung machines, which allowed you to stop the heart. The machine would carry on the work of the heart during the operation, you could stop the heart, open the chambers, and do these repairs. Now, this is a very complicated technology. The physiology of the heart and the lungs are difficult to replicate with a machine. And the patients in the early years of these devices suffered terribly. Patients would have strokes, they would have heart attacks, they would have seizures after surgery, and some patients would experience comas, or even brain death. And in the early years of open heart surgery, as many of a third of patients were having these neurological and psychiatric complications. So those weren't hard to notice, those were so visible. It was obvious to everyone involved in the field that these machines had these terrible risks. But the doctors and the engineers worked very hard, and after 10 years, the complication rates had been reduced substantially from maybe a third of patients to just, I say just, but just five or 10% of patients. So huge progress, but still a significant number of patients suffering these complications. But then an amazing thing happens. After 1968, when coronary artery bypass grafting get started, which was really the first of the successful surgical procedures for coronary disease, surgeons paid very little attention to the neurological or psychiatric complications of this procedure. I've looked at the first 200 articles that were published about this, and all of the articles will talk about how much the surgery relieved chest pain. A lot of them would describe that the procedure prevented heart attacks, or they hoped it would prevent heart attacks and make patients live longer. They paid attention to the cardiac complications, what percentage of patients died during surgery or had a heart attack during surgery. But of these 200 articles, only four of them discussed in a serious way the neurological or psychiatric complications. And that's despite the fact that all of these surgeons had been using heart lung machines for a decade, they all had seen these complications with other kinds of operations. They just didn't look for the complications with this one particular procedure. And you can say, well, that just seems like a small oversight, but the scale of the problem was enormous. By the mid 1970s, 100,000 patients per year were having coronary artery bypass grafting. It's likely, it's hard to know exactly, but it's likely that three to 5% of these patients were having strokes. So thousands of patients each year were having strokes because of these operations. And no one really appreciated that risk at that time. Looking back from the present, as an ethicist you could say, well, of all these people who consented for coronary artery bypass grafting in the first 10 years of that procedure, none of them gave proper informed consent because no one knew what their risks were. Their risks hadn't been studied. There was no way that they were informed. They were informed according to the knowledge that was available. But the knowledge that was available was terribly incomplete. And surgeons ought to have appreciated that at the time. So David, your book gives us this wonderful history about how cardiac care has evolved over the last several decades. And I'm wondering if we can look ahead to the future a little bit. Some of the emerging technologies that are coming along in personalized medicine or actually editing the human genome, are there lessons from the history that you described that might be informative to us as we move forward? So I think there are two main lessons. The first lesson is to be very careful about the intuitions we have about treatments and the need to collect very good data to test our intuitions. And the other lesson is to be careful about complications which are too often neglected by medical research. So in the case of personalized medicine, this is a series of treatments that make perfect sense. If you could predict a patient's response to a drug in advance, you could use that drug much more safely. But even though it makes sense, it's been very hard for doctors to produce evidence that it actually does work, that it does add value. And part of the problem there is that human genetics are really complicated. It's not just one gene that determines drug response. There might be 20 genes that are relevant. So testing a single gene to predict response just isn't going to work. Even though the intuition is obvious, the reality is more complicated. And in terms of complications, the cardiac history shows the doctors are at risk of focusing on the desired benefits and neglecting the complications. And you see that exactly with the research and the journalism coverage of CRISPR. There's enormous focus on the fact that these have tremendous power to fix mutations and to solve these problems. And you can actually show quite easily that that indeed is possible. You can edit a gene so that a cell that couldn't make a protein now can make a protein. But everyone knows that this technology is at risk of off-target mutations. It fixes the gene you want, but then it also randomly adjusts a few other genes. It's very hard to detect that. To know the full rate of off-target mutations, you'd have to sequence the entire genome. And that isn't done very often. And so doctors often don't study thoroughly the risk of off-target mutations, and therefore they're underestimating the complication rates. From the data we do know, this is a serious problem. One study over the summer showed a 25% risk of off-target mutations. Potentially that's a 25% risk of cancer in patients who have this intervention. And that's something that at this point few patients would be willing to sign up for. Wow, you've really made a very convincing case that the lessons from the history of cardiac care have much to teach us about the new technologies that are coming along today. I'd like to thank you, first of all, for the scholarship in the book. It's a huge contribution to our understanding of how medicine develops. It's a very enjoyable book to read. I personally developed many insights from that. And I'd also just like to thank you for being with us here today and sharing some of your thoughts about the book and where things are going in the future. So thank you very much, David. It's wonderful to have this opportunity to make the case for why history can be a valuable part of medical knowledge and decision-making. And thank you all for watching the interview and participating here. We would like to invite you to go to our website and to see the full book review of Professor Jones' book that is authored by Diana Alame and also check out the other things that are on our website, both at the Harvard Medical School Bioethics Journal as well as the Harvard Medical School Center for Bioethics. Again, thank you for joining us.