Muralidhar Padala Receives Two R01 Grants Totaling $5 Million to Develop Novel Techniques to Repair Diseased Heart Valves

August 2017

Muralidhar Padala, PhD, director of the structural heart research program of the Emory Cardiothoracic Research Laboratory, has been awarded two National Heart, Lung, and Blood Institute R01 grants totaling $5 million to develop new techniques to repair mitral regurgitation in patients with heart failure. Mitral regurgitation occurs frequently in these patients due to enlargement and dyssynchrony in their left ventricles, and presents as the backwards leakage of blood through the mitral valve with each left ventricular contraction.

The first award is for a five-year, $3.2 million study, "Novel therapeutic approaches to repair ischemic mitral regurgitation," which will focus on translating papillary muscle approximation (PMA), an inventive mitral valve repair technique that Dr. Padala's laboratory has studied extensively, to implementation in humans. PMA preserves and restores papillary muscle function by drawing the muscles closer together with an encircling loop.

The desire to develop PMA had its beginnings in a paper published by Dr. Padala's group in the November 2014 edition of Journal of the American College of Cardiology (Kalra K, Wang Q, McIver BV, Shi W, Guyton RA, Sun W, Sarin EL, Thourani VH, Padala M, JACC, 2014, 64(18): 1867-79). The study demonstrated that dynamic separation between the two papillary muscles of the heart indicates the severity of mitral regurgitation prior to repair, and that undersized mitral annuloplasty—the current gold standard of valve repair that involves the implantation of a device that tightens around the valve and pulls the leaflets together—had poor durability when implemented in patients with elevated inter-papillary separation.

Continuing from that study, Dr. Padala's group replicated mitral regurgitation in swine and performed a pre-clinical trial comparing PMA to mitral annuloplasty. The study documented PMA's positive results and formed the basis for the new human study.

Dr. Padala will lead the study, in collaboration with cardiothoracic surgeon Robert Guyton, MD, cardiologist Stamatios Lerakis, MD, MR imaging expert John Oshinski, PhD, and cardiac anesthesiologist Michael Duggan, MD.

The second award, a four-year, $1.8 million study entitled "Transcatheter approaches for leaflet extension to repair mitral regurgitation," will concentrate on conducting extensive bioengineering and pre-clinical studies to advance a new image-guided, transcatheter mitral valve implant developed in Dr. Padala's laboratory. Called the MitraPlug, this innovative technology consists of a miniature nitinol implant mounted on the tip of an image-guided catheter and deployed onto the mitral valve leaflet to extend its shelf and restore proper closure.

"The MitraPlug could provide an option for repair of valvular regurgitation in heart failure patients who may be too sick to undergo surgery," says Dr. Padala. "If we succeed in safely and effectively treating these patients, it could compete as a less invasive option for traditional surgical patients as well."

As the inventor of the technology, Dr. Padala will lead this study in collaboration with Dr. Guyton, Dr. Duggan, and Eric Sarin, MD, of the INOVA Heart and Vascular Institute.

"We are very excited for Dr. Padala and his team that the NIH has made considerable investments in translational research in our cardiothoracic research laboratory at Emory," says Michael Halkos, MD, chief of the Emory Division of Cardiothoracic Surgery. "With the diverse expertise that Dr. Padala and his team are developing, they are moving laboratory research into clinical practice, and making our clinical surgeons key stakeholders in the process."

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