Distinguished Scientist Describes a Fine-Tuning Approach to HF Michael Bristow, MD, PhD, FACC, has spent decades studying and building therapies off the various mechanisms of heart failure. “Many things can lead to [heart failure],” says Bristow, who is a professor of medicine/cardiology and director of pharmacogenomics at the University of Colorado Cardiovascular Institute. “But there are final common pathways when the heart really begins to fail – at least with systolic dysfunction – that cross a broad range of inciting etiologies and the failing heart muscle looks the same biochemically, molecularly, and so forth. This is why some of the treatments that have been effective work regardless of what started the process.” One of Bristow’s most regularly cited accomplishments took place in the early ‘80s when he looked at the status of ß-adrenergic pathways in failing hearts. “We found something completely different from what the dogma at the time was, which was that a failing heart was overstimulated by adrenergic drive,” recalls Bristow. “We knew that adrenergic over-stimulation was not likely to be helpful long-term and was most certainly harmful based on other studies we had done. So we began to be convinced that the way to deal with this was to block that adrenergic stimulation, but the trick was, how do you do that when the patients are also using adrenergic stimulation to support their failing heart? How do you back that off slowly? We and others figured out how to do that by starting with tiny doses of ß-blockers and slowly titrating up.” With his efforts culminating in the approval of the first ß-blocker for the treatment of heart failure, Bristow has continued to enhance the field’s understanding of the cellular and molecular pathways that play a role in the regulation of cardiac receptors and the role of ß-adrenergic receptor genotypes in modulating receptor function and patient response. Currently Bristow is overseeing the development of genetically-targeted therapies for cardiovascular diseases, with one particular drug – bucindolol hydrochloride – having the potential to be the first prospectively developed genetically targeted cardiovascular drug, in this case for atrial fibrillation prevention treatment in heart failure patients. “My outlook is obviously quite positive, and is frankly based on the progress that we’ve made in the past 25 to 30 years,” says Bristow. “Now the challenge is to fine tune the anti-adrenergic approach.” Cardiac Electrophysiology Pioneer Dedicates Career to Correcting Heart Beats Melvin Scheinman, MD, FACC, has spent a lifetime making the heart beat just right. One of the pioneers of cardiac electrophysiology, Scheinman is best known for performing the first catheter ablation in humans. “Before if someone had a very erratic rhythm the only thing they could do was open the chest and destroy the region at fault with direct surgical means,” says Scheinman. “So I thought of the idea of putting a catheter in and doing something similar to what the surgeons do.” Raised in Brooklyn, NY, Scheinman earned his undergraduate degree at Johns Hopkins University, demonstrating his drive and academic acuity early by graduating first in his class. While obtaining his training in cardiology at the University of California, San Francisco (UCSF) Medical Center – where he still works as a professor of medicine – Scheinman was briefly in charge of the Coronary Care Unit of San Francisco Hospital. It was at this sister facility that Scheinman was exposed to a bevy of patients with heart rhythm disorders. As the tools for the invasive evaluation of these patients were just starting to develop, Scheinman took interest and branched into electrophysiology. To this day, Scheinman still remembers the first patient to undergo his invented therapy in March 1981. “The patient was an oil refinery worker and had heart failure and severe rheumatoid arthritis so he wasn’t a candidate for surgery,” explains Scheinman. “The surgeon felt that he would never survive the post operative period due to his severe comorbidities. We had done work in dogs three years prior and when this patient came along, after institutional review board approval, he said, ‘Get on with it,’ and fortunately it worked.” These days, investing himself in teaching and clinical research, focusing on patients who are born with predispositions to serious rhythm disorders at UCSF Medical Center’s Comprehensive Genetic Arrhythmia Program, Scheinman has remained an invaluable resource in the ever expanding practice of heart ablation. “The field has grown exponentially,” says Scheinman. “In more recent years, techniques have been developed to extend ablative procedures to very complicated rhythms in very sick people. Mine was just the first step.” Mathematician Explores Heart Stem Cell Regeneration While many of his undergraduate peers were pursuing pre-med degrees in biology and molecular genetics, Eduardo Marbán, MD, PhD, FACC, took a less strategic approach, majoring in mathematics. Regardless of where he started, practicing medicine was always the end goal for Marbán, who has since become one of the most prominent cardiologists in the nation, serving for 25 years at Johns Hopkins University School of Medicine – working his way up from intern to chief of cardiology – and is currently the director of Cedars-Sinai Heart Institute in Los Angeles, CA. Among Marbán’s myriad of honors and accomplishments, perhaps the most influentially significant is having successfully used the stem cells from a patient’s own heart to regenerate and repair seemingly irreversible tissue damaged by a heart attack. “The standard teaching with a heart attack has been that it’s not possible,” says Marbán. “However, we found that when you give patients who have had a heart attack stem cells from the heart, the scar shrinks and the amount of living heart muscle increases.” With his research progressing into a phase two, 300 patient, randomized, placebo controlled, double-blinded study, Marbán believes that there isn’t any reason why the paradigms that he’s developed in the heart couldn’t be translatable to other organs.”It’s exciting because obviously it raises a whole lot of therapeutic applications in cardiology, but it also raises the general prospect that some of these settings might be where we can also coax the body into rekindling its own repair mechanisms,” he says.
Published by American College of Cardiology. View All Articles.
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