Distinguished Scientist Describes a Fine Tuning Approach to HF

Cardiology Magazine Fall 20143 Distinguished Scientists | 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 β-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 β-blockers and slowly titrating up.”

With his efforts culminating in the approval of the first β-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 β-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.”

Keywords: Cardiology Magazine, ACC Publications

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