A tale of two doctors

John Elefteriades

The walls of his office are lined with a variety of “Best Doctor” magazine covers and plaques from professional societies. But John A. Elefteriades, M.D. ’76, HS ’81, FW ’83, directs visitors’ attention only to the framed pages closest to his desk. They are thank-you letters and drawings from patients, famous and less well-known, whom he has saved in the operating room. Congratulate Elefteriades on one of his latest accolades, being named the William W.L. Glenn Professor of Cardiothoracic Surgery in 2006, and he’ll smile slightly and call the appointment “some kind of clerical error.”

Cardiologist Lawrence S. Cohen, M.D., HS ’65, the Ebenezer K. Hunt Professor of Medicine and a longtime mentor and collaborator, sets the record straight. Glenn, who died in 2003, was a pioneering surgeon, head of the cardiothoracic section for decades, and one of Elefteriades’ teachers. “He was very proud of John and hoped that after the chair was established that John Elefteriades would be its first incumbent,” Cohen said.

Elefteriades has done groundbreaking research on aortic aneurysms—weakened areas in the wall of the heart’s main artery—and is sought out by millionaires and royalty for his surgical skills. But Cohen says patients are just as often moved by “his gentleness.” Patients like Carmela Kolman.

Kolman was 32, an artist who knew that she had an aortic aneurysm and that it meant surgery at some point in her future. The future came crashing down on her, however, one Saturday morning in 1993 when the three layers of tissue comprising her aorta were forced apart by the pressure of the blood inside the vessel and the aneurysm dissected. She crawled to the telephone and whispered to the 911 operator, “Pain. In my chest.”

Elefteriades repaired her aorta and became a “calm, reassuring presence” in the weeks that followed, both for Kolman and her husband, John A. Rizzo, Ph.D., a health economist then on the faculty of the Department of Epidemiology and Public Health. Together Rizzo and Elefteriades embarked on a course of research that continues to improve care for patients like Kolman.

Despite the danger of aortic aneurysms, physicians balk at performing open-heart surgery unless the aneurysm is at immediate risk of dissecting or bursting. But if the aneurysm does dissect or burst, mortality skyrockets. The key is determining the right moment to operate. There were few tools to predict when an aneurysm would reach a crisis stage until Elefteriades and Rizzo developed the largest aortic aneurysm database in the world, with 3,000 cases. In the past 15 years, their research has identified the risk factors that put patients with aneurysms in imminent danger.

Rizzo, now at the State University of New York at Stony Brook, jokes that Elefteriades is “the only person I’ve ever worked with for an extended period of time who has never lost patience with me.” But he goes on to say that Elefteriades never loses patience, period. When the data are perplexing or a journal imposes an impossible deadline, Elefteriades maintains perfect composure, Rizzo says, and the calm is contagious. “That’s what I call a leader,” he adds.

Elefteriades also collaborates with the Celera Group, the private firm that engaged in a scientific race with the government’s Human Genome Project. Together they’ve identified genetic alterations associated with aneurysms and, by examining a patient’s RNA, can predict whether a patient will develop an aneurysm. (Their findings were published in the October 17 issue of PLoS ONE.) The test is 85 percent specific and close to 100 percent accurate, meaning that positive results accurately predict the development of aneurysms while about 15 percent of the patients on track for an aneurysm will test negative. DNA analysis that could complement the RNA findings is under way, and Elefteriades hopes the test will be widely used in high-risk patients.

His research has also taken him into the twilight zone where patients hover on life’s threshold. To operate on the aortic arch—the area usually clamped off when a patient is put on a heart-lung machine—blood circulation is suspended by inducing hypothermia. When a patient’s body cools to 18 degrees Celsius (about 64.4 degrees Fahrenheit) and the metabolic rate slows to 12.5 percent of normal, Elefteriades has 30 to 60 minutes to repair an aneurysm on the aortic arch. His patients have neither blood pressure nor pulse; they are “for all intents and purposes, dead,” says Elefteriades. They awake with no apparent loss of memory or cognitive function.

“I’ve done [the operation] probably as much as anyone has done it,” says Elefteriades. “And I don’t understand it. I’m awed by it.”

He wants to know why these patients thrive after a brush with death. He has an undergraduate interviewing 75 patients and their spouses in search of “subtle aberrations” in the patient’s behavior after the surgery. The patients selected for the study have varied but mentally demanding occupations: there are lawyers, doctors, artists and financial analysts in the sample. The study found no decline whatsoever in their functional state after deep hypothermic arrest, Elefteriades said.

Elefteriades continues to publish on the health risks of an exercise he enjoys himself, weight lifting. He has seen patterns in sudden deaths among high school and college athletes who lift weights, an exercise Elefteriades first took up as a high school wrestler. He reviewed cases of 31 young men who had died when their undetected aortic aneurysms dissected. He is recommending echocardiograms for all weight lifters to screen for aneurysms. Elefteriades acknowledges that the recommendation drives up health care spending but says, “I don’t know any other way to keep these kids safe.”

His research tends to spring from clinical questions, so in a sense the surgeon’s own heart never quite leaves the operating room. “The operating room is like a drug,” he says. “If I’m away for a week, I feel I haven’t contributed to humanity.”

Ironically, the career that inspires such passion in him was the result of happenstance.

A top student and serious wrestler on the high school team in Lansdowne, Penn., Elefteriades had been accepted to the Massachusetts Institute of Technology. He was planning to be an engineer, much to the pride and delight of his immigrant parents, who had not gone to college themselves. One day a Yale recruiter walked into his classroom and declared, “Young man, you’re going to Yale.”

Elefteriades says he does not know what piqued the recruiter’s interest—perhaps a chat beforehand with the friendly principal. Whatever the reason, he is grateful that fate steered him to New Haven.

At Yale, his horizons widened. “I think it’s the best place to go to college that there is,” Elefteriades remembers. Yale allowed him to follow his varied interests: French literature, physics, psychology. It wasn’t fashionable to have a career path in mind in the early seventies, he recalls. So he began taking exams for various graduate and professional programs. He ended up in medical school because the MCATs were the first set of results he got back.

He explains his choice of surgery as motivated by “a love of the beauty of the body, and the body really is beautiful—internally, externally.” He remembers the world of cardiothoracic surgery in the 1970s being relatively new and full of challenges. While much of his work involves expanding the discipline’s knowledge base, he is equally satisfied performing bypass surgery, though he’s done the procedure thousands of times. “Each case is a little different. Every blood vessel is a little different,” he says.

In addition to his scholarly work, Elefteriades writes for the lay public, a pursuit he finds “relaxing.” He coauthored Your Heart: An Owner’s Guide with Cohen, a work that explains cardiac problems and their treatment. Both writers said the book is in part a response to the time pressure exerted by health management organizations that frequently robs patients and families of the chance to ask detailed questions of their physicians. A second book, The Woman’s Heart: An Owner’s Guide, is in press. Elefteriades, who co-authored the book with Teresa Caulin-Glaser, M.D., a clinical associate professor of internal medicine at Ohio State University, hastens to explain that he’s demystifying the female heart from a medical perspective, not a poetic one. “If I could understand the woman’s heart, that would be great,” he says. “I think women are much more complex and interesting than men—emotionally and in nearly every other way.” He also has a book on cardiac fitness in the pipeline and another of patient stories, titled Extraordinary Hearts.

He attributes his productivity to a “phenomenal” support staff and a changing corps of students and residents who do much of the heavy lifting in his research. “My role as a mentor is to identify a topic that is an important open question,” says Elefteriades, and then to offer guidance on how to write a scientific paper. He finds that students “usually exceed any expectations I could have for them.”

Elefteriades received the Socrates Award for Excellence in teaching and mentoring of residents from the Society of Thoracic Surgeons in 2006. He calls his impact as a teacher his proudest achievement and points to the former Yale residents who are now directing cardiac centers.

It is especially gratifying to bring a medical student into the operating room for the first time and hear, “This is the greatest day of my life!” That was how Elefteriades felt his first day in surgery. The feeling has lingered.

Lawrence Cohen

When Jeffrey R. Bender, M.D., HS ’83, met Lawrence S. Cohen, M.D., HS ’65, in the early 1980s, Bender was a resident in internal medicine and Cohen introduced Yale medical students and residents to cardiology. Deliberate, concise and impeccably dressed in a blazer, collared shirt and cuff links, never a crease out of place, Cohen was one of those professors whom students honor with a nickname.

“He was known as ‘Larry the Heart,’ ” recalls Bender, now the Robert I. Levy Professor of Preventive Cardiology and professor of medicine and immunobiology, “and he was the consummate teacher.”

At 74, Cohen, the Ebenezer K. Hunt Professor of Medicine, is still the expert from whom every Yale medical student learns how to listen for and interpret heart sounds. He estimates that he’s taught some 3,000 students over the past 35 years. But that facet of his academic life represents just a fraction of his contributions to Yale, to medicine and to the advancement of cardiac care during a career that began with his graduation from New York University Medical School in 1958.

It’s advancement of patient care that fills Cohen with satisfaction and even a sense of wonder when he thinks back to the early days of his academic career. “The number one difference between then and now is that someone practicing now has the tools to prevent heart disease,” he says. That we have this armamentarium at all is in part thanks to Cohen. The Brooklyn-born cardiologist was a key player in the major studies that established the efficacy of clot-busting medications to stop heart attacks and slow the hardening and clogging of the arteries that usually precipitate coronary disease. Cohen was the principal investigator at Yale of a series of multicenter trials of thrombolytic drugs, including streptokinase and tissue plasminogen activator, or t-PA. These drugs dissolve blood clots by harnessing an enzyme called plasmin to break down fibrin, the protein that helps platelets bind to form a clot. These early Thrombolysis in Myocardial Infarction (TIMI) trials in the late 1980s proved that thrombolytics would help patients who were experiencing an acute myocardial infarction, an interruption of blood flow to the heart muscle. Since the mid-1970s, Cohen has overseen some two dozen trials of heart disease treatments, some of them ongoing.

Because of his wide experience and calm, effective approach to decision making, Cohen’s advice has been sought for years. Students, residents, fellows, colleagues in cardiology and deans trust his judgment, and not only about medicine. In 1991, then-Dean Leon Rosenberg, M.D., HS ’63, asked him to serve as his deputy dean. Cohen continued in that role under Robert Donaldson, M.D., and Gerard Burrow, M.D. ’58, HS ’66. For the past 10 years he has been the special advisor to three deans, David A. Kessler, M.D., Interim Dean Dennis D. Spencer, M.D., HS ’77, and current Dean Robert J. Alpern, M.D., Ensign Professor of Medicine. Cohen’s focus has ranged from overseeing faculty appointments and promotions to raising money for endowed professorships to investigating scientific misconduct and fraud. Of the latter, Cohen says, “It doesn’t happen very often, but when it does the university takes it very seriously.”

With his colleague Merle Waxman, M.A., the medical school’s ombudsperson, Cohen took a preventive approach to research misconduct. They developed a seminar series titled “The Responsible Conduct of Research,” which has been presented to more than 1,000 postdoctoral fellows, graduate students and faculty since 1996. Most allegations, Cohen believes, can be avoided by taking a few precautions, and he advises faculty to be open and communicative about their research from the earliest stages of a project. Meticulous and transparent data recording, frequent meetings with collaborators and familiarity with all aspects of a project, not just one’s own part in it, he says, are the keys to avoiding problems down the road.

After 16 years, Cohen stepped down from his role as the dean’s advisor last July, but he is continuing as a full-time faculty member and practicing cardiologist. “I’m not retiring,” he told colleagues and acquaintances in the weeks leading up to a May 1 reception in his honor in the Medical Historical Library. As word of the reception spread, Cohen found himself explaining again and again that he was not leaving Yale.

“I hear you’re retiring,” Don McNulty, a maintenance worker that Cohen has known for 30 years, said a few days before the ceremony, which was attended by more than 100 colleagues, family members and friends, including Yale President Richard C. Levin and Yale-New Haven Hospital CEO Marna P. Borgstrom, M.P.H. ’79.

“I’m not retiring,” Cohen said for the umpteenth time, his face betraying not a hint of impatience. “I’m just leaving the dean’s office. I will still be here.”

That’s good news for the medical school, says longtime collaborator John A. Elefteriades, M.D. ’76, HS ’81, FW ’83, the section chief and William W.L. Glenn Professor of Cardiothoracic Surgery. Elefteriades, who learned from Cohen to listen to the heart as a medical student, calls his mentor “the cardiologists’ cardiologist.”

“When any of us is ill, we go to him,” he says of Cohen. “Both my parents see him. Whenever there’s a tremendously difficult or complex case that requires exceptional judgment, cardiologists from all over the region will send their patients to him.”

In 2007 Elefteriades and Cohen published their second book together, Your Heart: An Owner’s Guide (Prometheus Books), with a foreword by artificial heart inventor Robert Jarvik, M.D. It is Cohen’s fourth book—he has also published 34 book chapters and 136 papers.

Cohen is married to Jane A. Cohen, M.S.W., a psychiatric social worker in private practice, and has two daughters and four grandchildren. He grew up in the Flatbush section of Brooklyn, N.Y., the youngest of three children. His grandparents were emigrants from Poland and Russia; his father owned a chain of men’s clothing stores. Cohen attended Midwood High School in Brooklyn and then Harvard College, graduating in 1954 with a degree in social psychology. After medical school at NYU, he came to Yale in 1958 as an intern in medicine and stayed for a second year as a resident before joining the U.S. Public Health Service as a research fellow in infectious diseases. After two years as a research fellow in cardiology at the Peter Bent Brigham Hospital in Boston, he returned to Yale as a senior resident in 1964-65.

His mentors were Paul B. Beeson, M.D.; Eugene Braunwald, M.D.; and Donald W. Seldin, M.D. ’43, HS ’46. Cohen remembers Beeson, a legendary chair of medicine at Yale who conducted research on fever and discovered the class of signaling molecules called cytokines, as “a quiet, charismatic man who led by making you want to do your very best.

“You never wanted to disappoint Paul Beeson. He really cared about the care of the patient and would sit down on the bed and talk directly to the patient, which was very unusual in that day,” Cohen says. Braunwald, author of the leading cardiology text, Heart Disease, and chair of the TIMI Study Group at Brigham and Women’s Hospital, recruited Cohen to the cardiology branch of the National Heart Institute, where Cohen served as chief of the clinical service. He would go on to work with Braunwald on the first three TIMI studies, which proved that heart attacks are caused by the rupture of plaque from the wall of an artery, followed by clotting.

“It was the clot that stopped the blood flow and caused the death of heart muscle,” says Cohen. “TIMI proved that if you could dissolve the clot in a timely fashion and thereby re-establish blood flow to the heart muscle, you could limit or prevent the effects of a heart attack completely.”

Seldin, who left a comfortable teaching post at Yale to build a research powerhouse at the University of Texas Southwestern Medical School, recruited Cohen to Dallas. After two years, Cohen was lured back to Yale in 1970 as chief of cardiology.

Trained by giants in medicine, Cohen has himself mentored dozens of influential cardiologists and leaders in academic medicine, including Kim A. Eagle, M.D., HS ’83, director of the Cardiovascular Center at the University of Michigan; and John M. Lasala, M.D., Ph.D., FW ’90, director of interventional cardiology at Washington University in St. Louis.

Lasala, who came to Yale as a cardiology fellow in 1986, remembers being impressed by Cohen’s ability to find the most salient and critical details in a mass of complex information. “He obviously knew quite a bit, but the most amazing thing was his ability to synthesize great amounts of information into simple and factually correct assessments,” says Lasala. He recalls examining a patient who had been seen in the practice 20 years previously. “Whose notes do you think were in the chart?” Whereas some of the notes would run to two or three pages, he says, “Larry’s notes were three lines—but much more informative. They were so pithy and to the heart of the matter—no pun intended—that you couldn’t fail to be impressed. He could say an awful lot with very little.”

Eagle recognized this ability as well, along with Cohen’s penchant for relating to patients. “He’s brilliant,” Eagle says. “He doesn’t go through the motions but focuses entirely on each patient, and he finds things that other doctors don’t find. He’s meticulous, not only in his speech, dress and manner, but in his physical examination. He’s like a laser-guided missile when it comes to finding a problem.”

Cohen is looking forward to his continued work with patients, students and trainees and his work on the medical school’s admissions committee, on which he has served for the past six years. He’ll continue teaching for the satisfaction of inspiring young people and watching them grow, he says, and he’ll remain active academically because of the stimulation it provides. “The collegiality and contact with people who are pushing the frontiers of science—that is a very good feeling,” he says.

But his voice takes on a tone of reverence when he speaks of his work in the clinical realm.

“Being able to make a difference in patients’ lives,” Cohen says, “is a privilege.”