Early Childhood and Influences
E. Magnus Ohman, MD: Hello. I'm Magnus Ohman from Duke University in North Carolina. Welcome to another episode of the Life and Times of Leading Cardiologists. I'm very fortunate today to have my guest and friend, Dr Judith Hochman, who is the Harold Snyder Family Professor of Cardiology and Senior Associate Dean of Clinical Sciences at New York University School of Medicine in New York City.
I think most of the people who have interacted with you have realized that you've taken on the hardest clinical trials in medicine—the SHOCK trial,[1] the Occluded Artery Trial (OAT),[2] and now the ISCHEMIA trial. How did the endurance for these difficult trials arise?
Judith S. Hochman, MD: I have to go back to my childhood. First of all, I was very motivated to make a difference, and that goes back to an early age. We can psychoanalyze why that was, but in tenth grade, a biology teacher completely turned me on to science. His name was Mr Blank. We had an experimental curriculum on molecular biology, which was brand new back then. I said I wanted to be a research scientist. I did not go straight to medical school. I was actually in a PhD program before I went to medical school. I was going to cure cancer. I was going to do something very big, and that goal began in high school.
Dr Ohman: That's amazing. One teacher in high school turned this on. Tell me a little bit about your family. Are there any scientists in the family?
Dr Hochman: My father was a commercial chemist, making things like paints, inks, and glues. He became a chemist because he couldn't become a doctor. There were quotas back in the 1930s for allowing Jews in medical school, and he couldn't get into medical school in New York. He wasn't able to go outside of New York because of his very humble family upbringing.
My father was one of those parents that if you came home with a 98% on your report card, he asked what happened to the other two points. So, he was very much a motivator to always do better. My mother was also a big influence. She had a very strong sense of justice, about what was right and wrong and the need to make the world better, and that was passed on to me.
Dr Ohman: Fascinating. Were you the only child?
Dr Hochman: No, I had three older siblings. I'm the youngest, and I would say that was another motivator. They were all brilliant, very successful, and as the fourth child, I always felt like I would never measure up.
It's very funny. I grew up with this notion that fourth children were failures. So, I was extremely motivated to disprove that and to live up to my siblings who are all very successful. I became very tenacious and stuck with things no matter how hard they were. I think there's a lot in my childhood and upbringing that motivated me to do what I do.
Dr Ohman: I can see how some of those tenacious aspects have carried over to the clinical trials that we will discuss later.
I didn't realize that there were medical school quotas for Jews in New York City. Did this make you feel that if you didn't do well, you'd let your parents down?
Dr Hochman: The fact that my father couldn't be a doctor was definitely a part of it. It's interesting because I didn't go straight to medical school, and my siblings are not physicians either. But I think that did influence me—the fact that he had been thwarted. The discrimination was a motivator.
From Basic Science Research to Clinical Medicine
Dr Ohman: Where did you go after high school?
Dr Hochman: I went to Brandeis for college and then I went to Harvard graduate school and then Harvard Medical School.
Dr. Ohman: What did you do at Brandeis? What was your specialty?
Dr. Hochman: I was a biology major. Biochemistry and molecular biology.
Dr. Ohman: So, really going after your father. Almost identical.
Dr. Hochman: Yes. He was a chemist and I was a biochemist sort of. Molecular biologist.
Dr. Ohman: Fascinating. And then, graduate school at Harvard.
Dr Hochman: Studying cellular and developmental biology. My plan was to be a great basic research scientist and find a cure for something. That was my vision.
Dr Ohman: What made you switch to medicine from being in the molecular world?
Dr Hochman: Life is not only about big accomplishments. It's about the day to day—is your day-to-day work satisfying to you? I wanted more human interaction. Being in a lab, you interact with your colleagues and other graduate students and the professor, but working with test tubes is not the same as working with people.
It became clear to me that based on my personality and what satisfies me, I needed to do something more clinical. Hence, I went to medical school at Harvard. I was very fortunate that they took me. And then my path brought me to clinical research, which was the perfect combination of being a research scientist and working with patients directly.
I was able to combine the two, where I would feel satisfied based on hopefully large accomplishments but also the day to day.
Learning From the "Giants" at Harvard
Dr Ohman: How was Harvard Medical School? Was it as competitive as everybody says?
Dr Hochman: It was competitive, but there were some giants that you just learned a tremendous amount from and looked up to. Lewis "Lew" Dexter was one of those giants. He was an absolutely master clinician, and I learned the physical exam and cardiac exam from him.
Although it was competitive, the other students were often very supportive and collegial. Just the exposure to great physicians like Lew was very influential. As a medical student, Joseph "Joe" Alpert was head of the cardiac care unit (CCU). Eugene "Gene" Braunwald was the chair of the Department of Medicine, and I became an internal medicine resident under him, so he became a larger influence after medical school.
Dr Ohman: These early "clinical giants" were important. What happened during residency?
Dr Hochman: I was at Brigham. I was house officer and, of course, that was an incredible experience. The first day, I started in the CCU, and Dr Braunwald had one of his own patients in the CCU, which wasn't that common as he didn't admit that many patients under his name. He was chair of medicine and had a lot on his plate. But he had a patient in cardiogenic shock. And I was picking up this patient, and I would get frequent calls.
"Hello? It's Dr Braunwald." He wanted to know what the urine output was. He wanted to know all kinds of parameters. And, of course, that was quite a petrifying experience for a young, first-day intern.
Dr Braunwald had very high standards. He was certainly the kind of mentor and leader and chairman of the department that would make you strive to do better when you're a resident. He was tremendous.
Dr Ohman: He was very attentive to details, which is obviously asking all the right questions.
Dr Hochman: Absolutely. What I don't think people realize is that it takes not only asking great questions or knowing the bigger picture, but you really need to pay attention to the details, whether it's at the patient's bedside or in a clinical trial. Gene Braunwald was exemplary at that.
Dr Ohman: Your first clinical experience is very similar to my own on a cardiology rotation. Did you feel hopeless?
Dr. Hochman: At that time, we were enrolling in the Multicenter Investigation of Limitation of Infarct Size (MILIS) trial.[3] Intravenous hyaluronidase was one of the arms—there was no reperfusion, no percutaneous coronary intervention, no lytic agents. We did have balloon pumps. It was discouraging because the mortality rates were so much higher than they are now. But, on the other hand, it was motivating to make a difference, to make things better. The fact that I got exposed to research so early on in the CCU was probably highly influential in terms of an academic investigation path.
Dr Ohman: At the time, as I recall, there were only a handful of CCUs in the country randomizing patients in clinical trials.
Dr Hochman: Right. Brigham was one of those CCUs, so I was very fortunate to be there.
Choosing Cardiology and Influences at Johns Hopkins
Dr Ohman: Now you're a resident doing general internal medicine having to report to Dr Braunwald every day. Did you realize at this time that you wanted to be a cardiologist, or did it take a little bit longer?
Dr Hochman: No, it took me longer. I was actually very interested in the liver. I was thinking of gastroenterology.
Dr. Ohman: But, it's still metabolic, isn't it? Maybe your father's influence.
Dr. Hochman: You're very Freudian. I actually was going to take a gap year between residency and fellowship, which didn't happen. I needed to think about it a little more. I didn't make a decision to go into cardiology until the third year. After Brigham, I spent a year at the University of Massachusetts. It was called Brigham West. Jim Dalen and Joe Alpert were there, and Mo Greene, who was my chief resident, asked me instead of my third-year residency, instead of senior resident, to be chief resident. I was chief resident third year while Jim Dalen was basically setting up a new program. That was very exciting.
Dr Ohman: But then you leave and go to Hopkins. What made you pick Hopkins?
Dr Hochman: The division back then with Mike Weisfeldt leading it and Bernadine Healy running the CCU—it was so attractive. They were just incredible people and wonderful scientists and clinicians.
Dr Ohman: Bernadine Healy is a person I've heard you talk about before. She was really way ahead of her time. She was a female cardiologist who did some very innovative things. She was one of the first, right?
Dr Hochman: Yes. She was one of the giants in cardiology and was very forward thinking, as you said—maybe a little ahead of her time. She ruffled some feathers, but she was a wonderful mentor to me. I worked in her lab, studying infarct expansion, which is a process she described—thinning and dilation of the infarct zone, the substrate for aneurysms and global remodeling. She had me actually set up a rat model of myocardial infarction, which she had not used before. She used dogs, and it turns out that dogs have a lot of collaterals. You might get the coronary infarct zone to expand, and they're not very transmural. She was an amazing role model for me.
As many may not know, she then went on to the White House. She ran the Office of Science and Technology in the Reagan administration and later was the first female director of the National Institutes of Health.She ran for the Senate in Ohio, after moving there. She later married Floyd Loop, the cardiac surgeon from Cleveland Clinic, and then headed the Red Cross. She was obviously eclectic. She just had so many interests and had wonderful leadership skills.
Marriage and Children
Dr Ohman: Now you had some time for extracurricular activities at Hopkins too. Is that where you met your husband?
Dr Hochman: I met my husband at Hopkins. He was a fellow ahead of me and was actually assigned to show the fellows around the day I visited.
Dr Ohman: Was it love at first sight by any chance?
Dr Hochman: I think we were smitten. Yes, absolutely. We got engaged and married pretty quickly. We then had a child—our first son, just about 11 months after we got married. He was born at Hopkins. Bernadine and Mike were terrific with me being pregnant as a fellow and later bringing the baby in. I actually remember carrying him in one of these little portable bassinets, and I'd leave him next to Bernadine's assistant and go in and talk to her about my various manuscripts that were in progress.
Dr Ohman: You must have been one of the few cardiology fellows who were pregnant at the time, I would suspect.
Dr Hochman: Back then it was highly unusual, but now it's very common. It was highly unusual. Maybe I was the first one. But they were incredibly supportive. Actually, Bernadine threw a baby shower for me.
Dr. Ohman: Now, living in Baltimore--I guess this is in the '80s?
Dr. Hochman: Early 1980s.
Dr. Ohman: Was it violent, a little bit of unrest?
Dr. Hochman: There were some pretty bad neighborhoods, but the Inner Harbor had undergone renovation downtown—then there were neighboring parts that are still difficult and that were challenging. We lived by the undergraduate campus. It was very nice. Very lovely. The cost of living was very reasonable.
Dr Ohman: You're at Hopkins finishing your fellowship, and Richard, your husband, is a cardiologist too, right?
Dr Hochman: Yes, he was ahead of me in fellowship and before we met had committed to be chief resident at Cornell-New York Hospital. So, I was forced to go back to New York. Otherwise, I would have stayed at Hopkins or gone back to Boston. New York would not have been my first choice. But I've loved it. It's been great.
Dr Ohman: This is interesting coming from somebody who was born in New York City. Tell us why.
Dr Hochman: I had lived in Boston for 13 years and loved the size of that city. It felt more manageable. Growing up, I felt New York City was just too big. I wanted a little bit of a slower-paced lifestyle.
However, it was definitely worth going back to New York City to be with my husband, who has been absolutely my life partner, my rock—I can't say enough good things about him.
Back to New York City
Dr Ohman: What was your first job in New York?
Dr Hochman: I was fortunate and had three potential jobs, but I picked being at Columbia University Medical School and St. Luke's Roosevelt Hospital. Harvey Kemp, who did a lot of investigation on lack of obstructive coronary disease in women with myocardial infarction, was the chief of the division. It was a very supportive place.
Basically, I ran the CCU, and in terms of other expectations, it was just "go with it." I had a little lab. I studied myocardial infarction in a rat model. That's where I looked at late reperfusion, showing that late reperfusion inhibited expansion independent of salvage. It was amazing. It doesn't happen anymore where they set you up in a lab without any external funding. They said to just do the investigation that you want. That was amazing, but I found it hard to have a basic bench lab and run a CCU, and by then I had another child and another. It was a little difficult, and going into clinical investigation made a lot of sense to me.
Dr Ohman: The first trial you did was the SHOCK trial, as I recall. What was the starting point for this trial? What made you want to tackle cardiogenic shock?
Dr Hochman: Well, I had done some small late ancillary studies and the CAPTAIN study,[4] but I didn't write those protocols per se. I was not the study chair. I wanted to go for the biggest challenge. I wanted to go for a trial that I thought was going to make an impact. This is the highest-risk group of patients, and evidence was needed.
Subconsciously, maybe I was influenced by the fact that my mother died of a myocardial infarction and actually had right ventricular failure with single vessel right disease that couldn't be opened. She was just shy of her 78th birthday and died of right ventricular cardiogenic shock. Now, did that subconsciously influence me? Possibly.
Dr Ohman: That's amazing. Today, everyone knows the results of the SHOCK trial, and it is in all of the guidelines. It's one of the landmark studies that has been done. How did you then go to the next trial?
Dr Hochman: Next was OAT. OAT brought me back to bench research. What I had shown in the rat model when I first set up my lab in New York was that infarct expansion was inhibited, even with late reperfusion, too late to salvage any myocardium. So, I always thought this needed to be tested in patients. If you open the artery beyond the period of myocardial salvage, will that benefit the patient?
I had a hypothesis that it was going to benefit left ventricular remodeling, which was highly predictive of subsequent death. The trial couldn't be done until stents were invented because with plain old balloon angioplasty, the reocclusion rates for total occlusions, even subacute total occlusions, were very, very high.
Then, the Total Occlusion Study of Canada (TOSCA) trial[5] was published where stents reduced the risk for reocclusion, and we could go forward with OAT. By then, I had a network of colleagues all over the world. In fact, the LATE study[6] run by Eric Topol was tissue plasminogen activator vs placebo 6-24 hours after myocardial infarction. I had organized some ancillary studies with Paul Armstrong and Harvey White about this. I actually met Paul and Harvey this way. That was in the late 1980s, and we became great friends. It's great because you have an opportunity through one trial to develop friends and colleagues. You then build the next trial and the next and the next.
By the way, there is something I have to tell the young people about persistence. The SHOCK trial took me three submissions to the National Institutes of Health to get funding. The first time it was reviewed, it was sent back "NRFed"—not recommended for further consideration. That's how poor that one was.
Dr Ohman: That is probably one of the few failures that I've heard so far in your story.
Dr. Hochman: Well, you have to be persistent and tenacious. You use the criticisms, which were terrific. The way to improve your trials is to get other people to review them. I revised it and revised it again, and it finally got funded. The more eyes, the better. Peer review has some very positive aspects to it.
On Raising Children and Medical School Today
Dr Ohman: In this whole process, you're bringing up children. Did anyone go into medicine?
Dr Hochman: Yes, I raised three sons. The youngest, Ben, is a New York University medical student. He's a third-year student, and he loves it. We're delighted that one of our sons will be a doctor, assuming he graduates. He's on track and doing well. He is very interested in the brain, which I think is the new frontier.
Dr Ohman: How do you compare medical schools now to back when you were in school? What is the biggest delta that you can see?
Dr Hochman: Well, I am so surprised that medical school is now much more book learning and exam based. At the end of every core clerkship, they have these shelf exams. A lot of time during clinical rotation is spent studying for the shelf exams. There are only so many hours in the day, so I think they get less clinical exposure in general.
Dr Ohman: I think the clinical exposure is really key to develop as a physician, as most of the physicians go into the practice of medicine. I think it's very important in the whole upbringing of an individual who's going to spend most of their time talking to people. I share your concern that they may miss a few things.
Clinical Trials That Change Practice
Dr Ohman: Now, you're taking on probably the hardest trial ever done—the ISCHEMIA trial—randomly assigning patients to undergo an evaluation for ischemia. What made you come to this one? There's no animal model of this. In the practice of medicine, there are many questions for which we don't have answers. Answering these questions is actually the common theme of all of your trials.
Dr Hochman: Yes, it's to answer the unanswered clinical questions. I was actually very surprised by COURAGE[7] and BARI-2D[8] because I did expect them to show benefit. Some were not surprised at all, but many cardiologists were surprised.
It really became an unanswered question with these negative trials. They didn't show superiority, but are there subsets of patients for whom we really should employ a routine invasive strategy? They didn't ask the question of whether you should do cardiac catheterization. All of the patients in those trials had cardiac catheterizations. To me, it was another natural question.
Dr Ohman: It's interesting to me that a person of your stature and your ability to get into the details without actually knowing the extent of the anatomy, which is one of the aspects of the ISCHEMIA trial, that you as an individual could live with that yourself. Yet your trials have been so detail oriented. How do you juxtapose that?
Dr Hochman: I think one of the critiques of the COURAGE and BARI 2D trials is that the patients in the cath lab, where the interventionalist said they know the patient would benefit, never got randomized in the trial. It was very important to avoid that selection bias of those patients who are the best candidates for percutaneous coronary intervention never being randomized. That was critically important in the next trial.
We actually built in CT coronary angiograms that the core labs read, so someone knows that anatomy. It's not the study team, it's not the doctor, it's not the trial participant, and it's not us. But the core labs know that anatomy. In the end, we'll be able to look at anatomic subsets (if you have chronic kidney disease, you don't get the CT angiogram; there is room for clinical judgment with left main). We're learning fascinating things. For example, you can have core labs confirm at least moderate ischemia—10% or more of left ventricle—and have no obstructive coronary disease. So, cardiac syndrome X is quite real.
Dr. Ohman: And actually, that brings you back to Dr Kemp's research.
Career Advice for the Younger Generation
Dr Ohman: What advice can you give young people besides being tenacious like you in furthering their career? What is the biggest lesson that you've learned?
Dr Hochman: Follow your passion. Work hard. Become part of a team. Get yourself a small niche in which you're the expert. It's a combination of having some special expertise that you contribute to a team. Everybody, whether or not you're an "investigator," should be contributing to the answers to so many clinical questions for which we don't have a sufficient evidence base.
Dr Ohman: That's really good advice, especially from somebody who has given us so much. I think that's a great way of saying that there is always opportunity to find your area, and your area is to do the trials that really change practice. I want to thank you for participating with us today.
Dr Hochman: Thank you, Magnus. It's been a pleasure.
