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An Innovator at Heart

08/13/2015

Assistant Director of the Interventional Cardiology Center and Investigator in the Molecular Cardiology Research Institute (MCRI) Navin Kapur, MD likes to think outside the box. An Interventional Cardiologist and Advanced Heart Failure specialist, his ingenuity and creative thinking have led to exciting new research, aimed at developing cutting-edge therapies for treating heart attacks and preventing heart failure. Dr. Kapur currently is leading two major projects that potentially have widespread implications for the care of cardiac patients.

Pursuing a Treatment for Cardiac Fibrosis

Working in the Molecular Research Lab, Dr. Kapur identified a protein called endoglin (ENDO-glynn), which appears to have a direct role in the development of cardiac fibrosis, a buildup of excess collagen in the heart, which stiffens the heart muscle and leads to heart failure. Dr. Kapur’s lab was the first in the world to show that endoglin appears to be a “master switch” that regulates both the way the heart responds to injury and the activity of critical proteins in the heart. Studying heart failure in a mouse model, Dr. Kapur and his colleagues showed that blocking endoglin improves survival by limiting the development of cardiac fibrosis and promoting the development of new blood vessels (angiogenesis).

To further advance this NIH-funded research, Dr. Kapur is working with several pharmaceutical companies to develop and study endoglin-targeting drugs as a new way to treat fibrosis in the heart and other organs.

“Early results from pre-clinical testing of these endoglin-blocking drugs look very promising,” said Dr. Kapur. “We soon hope to try the drugs on heart failure patients in clinical trials. Partnering with industry will help speed up the process. If we are successful, this therapy could be of great benefit to the eight million people in the U.S. and 24 million people worldwide who suffer from heart failure.”

An Immediate Solution to a Long-Term Problem

In the Interventional Research Lab, Dr. Kapur is using his clinical expertise in mechanical heart pumps to take a different approach to research on treating heart attacks. When an artery in the heart is blocked, reducing oxygen supply, the current standard of care is to open the artery as soon as possible to restore oxygen to the heart’s muscle cells.

“People survive with this technique, but the long-term ramifications are much less positive. A history of heart attack is associated with a five-fold increase in the incidence of heart failure over a five-year period and a recent study showed that as many as 75 percent of these patients develop heart failure within five years,” said Dr. Kapur. “We approached the problem from a new angle and instead targeted oxygen demand rather than supply.”

Through a partnership with medical device manufacturer Abiomed, the maker of the world’s smallest heart pumps, Dr. Kapur is exploring regulating oxygen supply and demand by using a heart pump called the “Impella” device to reduce the amount of oxygen the heart requires. By immediately inserting one of these pumps (in an eight minute procedure) in heart attack patients upon arrival at the hospital, the heart’s workload would be reduced and oxygen demand decreased. Approximately 30 minutes later, after the heart had a chance to rest, the blocked artery would be opened and normal oxygen supply restored.

Dr. Kapur’s lab tested this “mechanical conditioning hypothesis,” in an animal model and results showed an approximately 40 percent reduction in heart injury, compared to opening the artery alone without a pump in place. These pre-clinical findings are supported by medical registry data, showing that patients with a heart attack who receive the Impella device before opening the artery had improved short- and long-term survival rates. Now Dr. Kapur is working with Abiomed to develop a clinical trial to test the concept in humans.

“Our preliminary studies indicate that it may be important to first reduce the workload of the heart during a heart attack to decrease any damage to the heart and reduce the chance of developing heart failure in the future,” said Dr. Kapur. “The number of heart failure patients is projected to exceed eight million by the year 2030, resulting in $70 billion in health care costs annually. By using this novel approach to limit heart injury during an attack, we could be nearing a major breakthrough that could prevent the onset of heart failure, saving millions of lives and billions of dollars in health care expenditures.”

To learn more about the Molecular Cardiology Research Institute, please visit www.tuftsmedicalcenter.org/MCRI or contact the Institute directly at mcri@tuftsmedicalcenter.org.