Researchers to Study Why Epicardial Fat Triggers Atrial Fibrillation Differently Among Racial Groups

Fat deposits surrounding the heart have been linked to atrial fibrillation, a life-threatening irregular heartbeat. There are theories, but exactly how this “epicardial fat” increases risk remains largely unknown. An ongoing study aims to solve the mystery, identify new strategies for treatment, and look for important distinctions among white, Black and Hispanic populations.

Jeffrey Goldberger, M.D., a cardiac electrophysiologist and professor of medicine in the Division of Cardiovascular Medicine at the University of Miami Miller School of Medicine, is the study’s co-principal investigator, along with Gianluca Iacobellis, M.D., Ph.D., a leading expert in epicardial adipose tissue and professor of medicine in the Division of Endocrinology at the Miller School.

The $3 million study was funded by the National Institutes of Health. Along with their collaborators, Dr. Goldberger and Dr. Iacobellis are enrolling 120 people with atrial fibrillation (AFib) and another 120 people without the disorder to act as controls. They will compare risk according to different epicardial fat levels shown on imaging and other parameters. The “Trans-omic Analysis of Epicardial Adipose Tissue in Atrial Fibrillation,” study is termed ‘trans-omic’ because it looks at proteomics, genomics and metabolomics in this adverse relationship.

Epicardial fat could have a direct effect on the heart because it sits directly on the left atrium, making it easier for substances to enter heart muscle. And similar to fat elsewhere in the body, this fat around the heart is not inactive.

“We know this fat can secrete what are called adipocytokines, which are substances that could promote fibrosis, inflammation and changes in ion channel function,” Dr. Goldberger said.

Racial, Ethnic Differences in AFib

Differences by race and ethnicity could reveal important clues. “It turns out that Black patients have less epicardial fat than whites. It also turns out that Blacks have less AFib than whites,” Dr. Goldberger said. “So it lines up.”

One unanswered question is: If lower-risk Black people do develop AFib, will imaging show they have epicardial fat levels similar to those of affected white patients? The researchers also plan to look for different biomarkers based on race and ethnicity.

“We know that epicardial tissue is different among different ethnic and racial groups,” Dr. Iacobellis said. “And that can also at least partially explain the different degree of cardiovascular risk related to each of these groups.” Differences in body fat distribution is another likely factor, he added.

With consent, the investigators will take biopsies of the epicardial fat tissue and subcutaneous fat in patients who are undergoing open heart surgery. They will evaluate these samples for relevant genes.

Among other questions: Are the profibrotic genes and inflammatory genes preferentially turned on in the epicardial fat compared to other fat tissue?

Another aim is to look at “metabolomics,” Dr. Goldberger said. Using CT scans and blood samples from large epidemiologic studies, the investigators plan to assess metabolites in the blood to identify any associated with epicardial fat and AFib.

An overarching study aim is to identify new therapeutic targets related to epicardial fat that can reduce risk of AFib moving forward. “At the same time epicardial tissue is a risk factor, it’s also a therapeutic target,” Dr. Iacobellis said.

Dr. Goldberger added, “We’re hoping that these studies that we’re doing will identify other targets that can be treated, because our current treatments are not so great.”

AFib Risk Can Be Modified

On a positive note, epicardial fat is a modifiable risk factor “in a lot of ways,” Dr. Goldberger said. For example, overall weight loss can be effective. Another trial from the same research team, the Liraglutide Effects on Atrial Fibrillation (LEAF) study, should reveal if the diabetes and obesity medication liraglutide added to risk factor modification reduces epicardial fat and improves the outcomes from catheter ablation as well.

Other classes of medications could also prove beneficial. “I am quite confident, because we already demonstrated with other studies that epicardial tissue is a very sensitive and highly responsive target of these medications,” Dr. Iacobellis said.

In addition to AFib, previous investigators have linked epicardial fat to coronary artery disease and heart failure. The study could change the paradigm for treating cardiovascular disease, Dr. Iacobellis said. “We hope, of course, that these will be groundbreaking results.” If so, that will provide evidence “that we can approach these diseases completely differently than before.”

The first phase of the study is expected to last 18 months to two years. About one third of participants have been enrolled to date. Researchers continue to recruit participants with persistent or paroxysmal AFib, particularly Black and white adults.

For more information or to refer a candidate to the “Trans-omic Analysis of Epicardial Adipose Tissue in Atrial Fibrillation” trial, contact Carlos G. Munoz Sterling at [email protected] or 305-343-6519, or Carmen Baez-Garcia at [email protected] or 305-243-3845.

Tags: atrial fibrillation, Dr. Gianluca Iacobellis, Dr. Jeffrey Goldberger, epicardial fat, National Institutes of Health