Correcting the Heart’s Rhythm
UCSF Dr. Vasanath Vedantham Researches Regenerative Heart Rhythm Therapies
by Hillary Hoppock
March/April 2019
Failure of the heart’s natural pacemaker is a common clinical problem that currently cannot be delayed or reversed. However there is promising medical research on the horizon for treatment of those suffering from heart rhythm disorders.
UCSF Dr. Vedantham is researching the heart’s pacemaking capacity. Image courtesy UCSF
Dr. Vasanth Vedantham, associate professor of medicine and cardiologist at University of California, San Francisco (UCSF), is pursuing research for regenerative therapies for patients with failure of the heart’s rhythm generator. Through a grant received under the 2019 National Institutes of Health’s New Innovator Awards, his lab at UCSF is focusing on the basic mechanisms that allow the heart to generate and maintain its own rhythm, in order to create the scientific foundation for reconstituting this essential function of the human heart for patients with failure of the heart’s rhythm generator.
A physician-scientist career path
Dr. Vedantham was interested in science from an early age. He received a bachelor’s degree in physics and master’s degree in biochemistry from Yale University, and initially planned a career as a pure research scientist. But he was also drawn to the human interaction in medicine and the immediacy with which physicians can relieve suffering and provide comfort. So, rather than choose between these two passions, Dr Vedantham committed to a career as a physician-scientist, which allows him to both take care of patients and work as a disease-focused medical researcher. He received support for this career path from the National Institutes of Health Medical Scientist Training Program, simultaneously earning his medical degree and his doctoral degree in neurobiology from Harvard.
Throughout his research career Dr. Vedantham has been fascinated by the mechanisms that allow different cells in the body to generate, conduct and transmit electrical signals, especially brain cells and heart cells. He explains, “With respect to heart rhythm, the human heart has evolved a sophisticated “wiring system” that controls how a heartbeat originates and spreads throughout the entire organ. Failure of the heart’s natural pacemaker is essentially an electrical problem in which the heart rhythm generator fails to transmit electrical signals to the rest of the heart at appropriate intervals, resulting in slow heartbeat.”
Approximately 200,000 pacemakers are implanted every year in the United States for patients with slow heartbeat. However, despite significant progress in developing new technologies for pacemaker and defibrillator devices, he notes, “We still require a battery-powered electronic device to detect the heartbeat and stimulate it with an electrode. While electronic pacemakers are often a life-saving treatment they can introduce their own set of problems and complications, and they leave patients with hardware inside their bodies for life. Patients often ask me whether there are treatments that can restore function to the heart’s natural pacemaker without the requirement for an artificial implant. Unfortunately, I have to explain that we don’t understand the biology well enough to design such a treatment.“
Inspired by this unmet need, Dr. Vedantham’s goal for the Innovator Award research is to take a more targeted, biological approach with an ultimate aim of using regenerative therapies for restoring heart rhythm to patients suffering from slow heartbeat, irregular heartbeat, and cardiac arrest.
A new therapeutic approach to slow and irregular heartbeat
Dr. Vedantham explains, “Slow heartbeat occurs when the specialized heart muscle cells called pacemaker cells (PCs) that reside within the heart’s natural pacemaking region, the sinoatrial node (SA), fail to generate enough current to activate the rest of the heart. Our hope is that we will be able to reactivate the biological pathways that control the embryonic development of this natural pacemaker in order to restore function to diseased sinoatrial node tissue, thereby doing away with pacemakers all together.”
Until recently, relatively little was known about the embryological origin of PCs and the molecular pathways controlling their formation. This is because each heart contains relatively few PCs (several thousand out of billions of heart cells), making them hard to find and characterize. Thus, a major hurdle in this field was developing methods to isolate pacemaker cells from the rest of the heart in order to dissect their molecular machinery. “Even if you excise the entire SA note from the heart for further study, only a tiny portion of the material you end up with (1-2 %) will consist of pacemaker cells,” Dr. Vedantham states.
However, a number of recent technological advances have allowed Dr. Vedantham’s lab to overcome this obstacle, rendering PCs easier to identify and isolate.
He reports, “Our lab has developed new approaches and tools using model systems that allow us to gather information about the signals and pathways that are active in guiding the formation, growth and function of pacemaker tissue throughout heart development. Specifically, we are able to label these cells with molecular “tags” that allow us to visualize them and genetically modify them.”
So, connecting the dots, this means his research team is poised to test whether delivery of genes and compounds required for pacemaker cell development to a diseased adult heart can reactivate the developmental pathways that create pacemaker cells in the embryo. Dr. Vedantham asserts, “In theory, this could allow for permanent regeneration of the heart’s pacemaking capacity without the need for artificial pacemakers or other treatments.” Hillary Hoppock is a freelance writer, former newspaper publisher and reporter based in Orinda, California.