Arnold M. Katz, MD
Arnold M. Katz was born in Chicago. His mother was a piano teacher; his father, Louis N. Katz, was an internationally renowned cardiologist and cardiovascular physiologist who received a Lasker award and was President of both the American Physiological Society and the American Heart Association. As an undergraduate at the University of Chicago, Arnold spent a summer at the Marine Biological Laboratory in Woods Hole, Massachusetts, where he participated in a study of the physico-chemical properties of skeletal muscle. As a medical student, he spent 2 summers in his father’s laboratory at Michael Reese Hospital in Chicago studying control of and interactions between coronary blood flow, left ventricular volume, and the energetics of the heart. In 1955, he first authored his first paper in Circulation Research on this subject.1 Thus, even before completing medical school, he had already worked in 2 areas—muscle chemistry and control of ventricular performance—to which he devoted much of his life as an investigator.
After receiving his MD cum laude from Harvard Medical School in 1956, Katz trained in internal medicine at the Massachusetts General Hospital. He spent 2 years in the Laboratory of Nobel Prize–winning biochemist Christian B. Anfinsen Jr, at the National Institutes of Health in Bethesda, Maryland, where he trained in and conducted research on protein chemistry. A paper on peptide separation and analysis, published in 1959 with Anfinsen, was identified by Current Contents as a Citation Classic.2 He then trained in clinical cardiology with Paul Wood, considered the leading clinical cardiologist of the era, at the Institute of Cardiology in London, followed by a 3-year advanced fellowship in muscle biochemistry with another distinguished scientist, W.F.H.M. Mommarets, at the University of California at Los Angeles (UCLA).
Thus, after training in basic science, clinical medicine, and cardiology with outstanding mentors, Katz began his faculty career in 1963 in the Department of Physiology at Columbia University. He moved to the University of Chicago in 1967 and, in 1969, returned to New York to become the first Philip J. and Harriet L. Goodhart Professor of Medicine (Cardiology) at the Mount Sinai School of Medicine. In 1977, he became the first chief of cardiology at the University of Connecticut School of Medicine, a position he held until 1998. After assuming emeritus status, Katz became Visiting Professor of Medicine and Physiology at Dartmouth Medical School, where he taught in several basic science courses. In 2008, he was also appointed Visiting Professor of Medicine at Harvard Medical School where he lectured on heart failure in the core curriculum. In retirement, he also returned to an early interest in the history of cardiovascular physiology and cardiology.
During his fellowship at UCLA, Katz described the physico-chemical properties of cardiac actin and tropomyosin and showed their striking similarities to analogous proteins obtained from skeletal muscle. He identified a role for tropomyosin in influencing the interactions between actin and myosin. He then focused attention on the role of Ca2+ on the interactions between the cardiac contractile proteins and the critically important role of variations in intracellular Ca2+ concentrations on the regulation of cardiac contractility. In a seminal paper, he demonstrated that the uptake of Ca2+ by the cardiac sarcoplasmic reticulum was sufficient, both in quantity and in rate, to account for relaxation of the intact heart.3 He characterized the bidirectional fluxes of Ca2+ across the sarcoplasmic reticular membrane. In later studies, Dr Katz’ research group provided important new information on the molecular structure of the Ca2+ release channel of cardiac and smooth muscle.
A major question faced by cardiovascular scientists in the 1960s was the mechanism by which β-adrenergic agonists exert their powerful inotropic and lusitropic actions. In 1967, Katz disproved one of the prevailing theories, namely that these agonists stimulate the contractile proteins directly. His laboratory and others showed that cAMP also did not have this direct effect. Subsequently, Katz and his colleagues discovered a 23 000 dalton protein (named phospholamban by his wife), which serves as a substrate for phosphorylation by protein kinase A.4 In a series of elegant experiments, they showed that the increased concentration of cAMP resulting from β-adrenergic stimulation causes protein kinase A–catalyzed phosphorylation of phospholamban. This, in turn, stimulates the ATP-dependent pump (SERCA) which returns Ca2+ to the sarcoplasmic reticulum, causing cardiomyocyte relaxation. This increases the Ca2+ content of the sarcoplasmic reticulum, making more Ca2+ available for release during the subsequent depolarization, thereby exerting a positive inotropic effect. Since this major discovery, a reduction of phospholamban content has been observed in experimental heart failure produced by mechanical overload, as well as in some patients with dilated cardiomyopathy.
Katz extended his intense interest in cardiac relaxation to the clinic, where he and his colleagues showed that the concentric ventricular hypertrophy in hypertensive patients is associated with slowed left ventricular filling, whereas the physiological eccentric hypertrophy in athletes is accompanied by normal or even accelerated filling. Another clinical extension of his bench research on cardiac relaxation resulted from the surgical description of the so-called stone heart. Katz explained that this usually fatal condition represented ischemic contracture resulting from depletion of ATP from the sarcoplasmic reticular pump, blocking reuptake of Ca2+ and therefore preventing relaxation.
In the 1990s, Dr Katz’ attention shifted to studies of heart failure that linked clinical cardiology to the basic sciences. He warned that chronic inotropic stimulation could prove to be detrimental to patients with heart failure and, conversely, that long-term administration of β-adrenergic blockers could benefit these patients. Both of these predictions were diametrically opposite to the then prevailing thinking, and both were proven to have been correct.
Katz published >400 original articles and edited or coedited >15 books. He was the sole author of 5 editions of Physiology of the Heart and one edition of Heart Failure: Pathophysiology, and Molecular Biology. Katz also published dozens of invited editorials, reviews, and book chapters, all models of clarity. He gave many named lectures at universities, national, and international meetings. I attended many of his lectures on the pathophysiology of heart failure which he gave to Harvard medical students each year and always came away excited and refreshed. It is fair to say that no cardiovascular scientist of the last half century has educated more students, trainees, scientists, and clinicians.
Katz was a serious student of the history of cardiac physiology and of cardiology. In 1957, just a year after graduating from medical school, he published a scholarly discussion of the knowledge of the circulation before William Harvey in Circulation. He also described cardiac disease at the time of Hippocrates, the influence of Ernest Starling and the “Law of the Heart,” as well as a history of the evolving concepts of heart failure. He provided a thoughtful discussion of the origin and early years of Circulation Research.5 In these and other publications, Katz brought keen insight into the forces acting on the field.
Katz served on the editorial boards of Circulation Research, the Journal of Clinical Investigation, and Circulation. He was the first elected Editor-in-Chief of the Journal of Molecular and Cellular Cardiology. Katz was a member of many academic societies and served as chair of the Basic Science Council of the American Heart Association, as well as of the Scientific Board of the Stanley J. Sarnoff Endowment for Cardiovascular Science. He was President of both the American Section of the International Society for Heart Research and of the Cardiac Muscle Society.
Katz received many honors, including the Research Achievement Award of the American Heart Association, the Distinguished Achievement Award of the Association’s Basic Science Council, the Distinguished Scientist Award of the International Society for Heart Research, and the Lifetime Achievement Award of the Heart Failure Society of America. In 1995, the American Heart Association renamed its young investigator award for basic research the Louis N. and Arnold M. Katz Prize.
Katz was one of a small number of important basic cardiovascular scientists who was also a well-trained and expert clinical cardiologist. He achieved enormous synergy from being a master of both disciplines. He applied to clinical cardiology the rigorous thinking characteristic of basic science. His clinical work, in turn, inspired much of his basic research.
Katz fought a serious illness for many years. Just a few days before his death, he and I had a long telephone conversation about his paper, which had just been published, on the mechanisms of contraction and relaxation in heart failure, in which he presented new insights.6
Arnold Katz is survived by Phyllis, his wife for 57 years, 4 children, 8 grandchildren, hundreds of friends, coworkers, and trainees, as well as many thousands whose understanding of cardiac physiology and pathophysiology was enriched by his efforts as a scientist, clinician, and educator.
- © 2016 American Heart Association, Inc.
- Katz AM,
- Katz LN,
- Williams FL.
- Katz AM,
- Dreyer WJ,
- Anfinsen CB.
- Katz AM,
- Repke DI.
- Kirchberger MA,
- Tada M,
- Katz AM.
- Katz AM.
- Katz AM,
- Rolett EL.