The 2015 Nahum J. Winer Lecture: “Heart Rate Modulation: Is it Therapeutic and if so for Whom?”

Heart rate is one of the most fundamental properties of the cardiovascular system, as it is a primary determinant of cardiac output and of myocardial oxygen demand. Further, there is a direct relation between the absolute magnitude of resting heart rate and the likelihood of cardiovascular adversities. However, it is not known whether alteration in heart rate beneficially alters outcome except in a small, though numerically important, set of cardiovascular disorders. With the relatively recent development of a pure heart rate slowing drug, ivabradine, 2 large clinical trials have been performed to determine the efficacy of heart rate lowering in chronic, stable CAD, with disappointing results. Conversely, among patients with systolic heart failure, the single large randomized controlled trial (SHIFT) revealed a marked reduction in hospitalizations for worsening heart failure and a clear trend toward reduction in cardiovascular mortality, reaching significance as the baseline heart rate increased in the affected subpopulations. On the basis of these results, ivabradine-based heart rate slowing has entered the standard armamentarium of treatment for patients with systolic heart failure, now numbering more than 3,000,000 in the United States. The data suggest that any beneficial effects of heart rate lowering are related to the underlying cardiovascular pathophysiology. Specifically, it appears that benefit can be expected when myocardial pathology is at least moderately severe, but not when coronary artery pathology predominates and the myocardium is normal. Thus, any role for population-wide heart rate lowering is of highly questionable validity. There the story might end were it not for a very recent trial in healthy mice, a species with a very high average heart rate and short life expectancy. In this study, survival was significantly improved by heart rate slowing with ivabradine. This report suggests that the end of the story has not yet been written. More studies and more data will be needed to place therapeutic heart rate slowing in its proper context for humans. 

About the Speaker

Jeffrey S. Borer, MD, is Professor of Medicine, Cell Biology, Radiology and Surgery at the State University of New York Downstate Medical Center. For 7 years he served as Chief, Division of Cardiovascular Medicine, simultaneously serving for 4 years as Chairman, Department of Medicine, at SUNY Downstate, administrative positions he has relinquished to concentrate on his work as Director of two research institutes at Downstate. Dr. Borer received a BA from Harvard, a M.D. from Cornell, trained at the Massachusetts General Hospital, spent 7 years in the Cardiology Branch, NHLBI, and a year at Guy’s Hospital (London) as Senior Fullbright Hays Scholar and Glorney-Raisbeck Fellow in the Medical Sciences, completing the first clinical demonstration of nitroglycerin’s utility in acute MI following his several years of preclinical studies at NIH. Upon returning to the NIH, he developed stress radionuclide cineangiography, enabling the first non-invasive assessment of cardiac function with exercise and importantly changing the practice of cardiology. He returned to Cornell for 30 years as Gladys and Roland Harriman Professor of Cardiovascular Medicine and Chief, Division of Cardiovascular Pathophysiology. At Cornell and now at Downstate, he performs clinical service, teaching and research, the latter primarily developing prognosticators for regurgitant valve diseases, and also has elucidated the cellular and molecular pathophysiology of these diseases. During the past 20 years he has also focused on assessing the effects of heart rate modification on clinical outcomes, with trials in coronary artery disease and heart failure. He has been an Advisor to the USFDA for 38 years, chaired the CardioRenal Drugs Advisory Committee for 3 terms and the Circulatory Devices Advisory Panel for one term, was a life sciences Advisor to NASA for 24 years, has served as officer/board member of several national professional societies (most recently founding President, Heart Valve Society of America 2004-2014, now expanded to the Heart Valve Society [international], of which he is a Trustee), has published almost 500 scientific papers and 6 books, has participated in various roles in numerous clinical trials of therapies, is editor-in-chief of the journal, Cardiology, and has received several awards and other recognitions for his work including, most recently, the Lifetime Achievement Award of the Heart Valve Society of America and Society of Heart Valve Disease of Europe (2014), and his selection as one of three Legends of Cardiology at the 10th Annual Complex Catheter-based Cardiovascular Therapeutics conference (2014). His research has been supported by NIH, AHA and, for many years, by several large private foundations.