NIH Grant Supports Innovative Multifaceted Heart Study

A new collaborative study led by a multidisciplinary group of investigators, most at the University of Miami Miller School of Medicine, and funded by the National Institutes of Health (NIH) will take a multifaceted approach to understanding how fatty tissue or epicardial adipose tissue around the heart can affect the risk of atrial fibrillation, a life-threatening irregular heartbeat.

“We will be analyzing genetic factors, blood markers, and metabolic factors associated with higher levels of epicardial adipose tissue surrounding the heart and atrial fibrillation,” said Jeffrey Goldberger, M.D., M.B.A., professor of medicine and chief of the Cardiovascular Division. “By analyzing these issues in different ways, we hope to lay the groundwork for more effective prevention and treatment strategies for this common heart rhythm disorder.”

Dr. Goldberger is the principal investigator in the multicenter study, “Trans-omic Analysis of Epicardial Adipose Tissue in Atrial Fibrillation,” developed in collaboration with the world’s leading expert in epicardial adipose tissue, Gianluca Iacobellis, M.D., Ph.D., professor of medicine in the Endocrinology Division at the Miller School.

The study is funded by a $3 million four-year NIH grant. Joseph Lamelas, M.D., chief and program director of cardiothoracic surgery, is leading the surgical acquisition of epicardial adipose tissue samples from patients who are undergoing surgery, which will provide unprecedented information. Other UM investigators include Joel Fishman, M.D., Ph.D., Noam Alperin, Ph.D., Gaofeng Wang, Ph.D., and Chuanhui Dong, Ph.D.

The NIH study also includes researchers from the University of Texas Southwestern Medical Center in Dallas, Case Western Reserve University in Cleveland, Northwestern University in Chicago, and the University of Rotterdam in The Netherlands.

Three areas of focus

Dr. Goldberger said the study will have three primary areas of focus, including an analysis of racial and ethnic differences in epicardial adipose tissue (EAT).

“We know that larger amounts of EAT may lead to inflammation and fibrosis, increasing risk for atrial fibrillation,” he said. “Blacks have lower buildups of that epicardial adipose tissue, and lower risk of atrial fibrillation. We will be looking at biomarkers and epicardial adipose tissue in those who do have atrial fibrillation.”

For this arm of the study, the Miller School researchers will enroll 120 patients with atrial fibrillation and 120 controls from the outpatient cardiology practice. There will be 40 White, 40 Black, and 40 Hispanic participants in each group.

The second arm of the study involves taking EAT biopsies from 60 patients undergoing cardiac surgery by Dr. Lamelas.

“We will look at those samples to see which genes might be turned on or off, compared with other parts of the body,” Dr. Goldberger said. If certain genes are activated, they may produce proteins that promote inflammation and fibrosis in the left atrial tissue, a precursor to atrial fibrillation.

The third arm of the project involves a retrospective look at blood samples, images and other data from three large-scale heart studies. Researchers will analyze stored blood specimens in the Multi-Ethnic Study of Atherosclerosis and the Rotterdam Study, as well as previously collected cardiac scan images and stored blood from the Dallas Heart Study.

“We will identify metabolomic correlates to EAT that predispose to atrial fibrillation,” Dr. Goldberger said. “We plan to leverage the findings from this multi-omic (proteome, metabolome, and transcriptome) approach to identify new approaches to treatment. Hopefully, this will lead to new targets for preventing the development of atrial fibrillation and treating this serious condition.”

Tags: Dr. Gianluca Iacobellis, Dr. Jeffrey Goldberger, Dr. Joseph Lamelas, epicardial adipose tissue, National Institutes of Health