Is adipose tissue just a matter of esthetics?

When fat becomes a problem

From a cardiologist's perspective, the real challenge is the epicardial adipose tissue, directly adjacent to the myocardium. Importantly, they are not separated by any anatomical barrier that would isolate this fat from the heart cells.

In a healthy body, epicardial adipose tissue performs an important protective function, e.g., protecting the heart from mechanical injuries. Regrettably, in the course of obesity or diabetes and under the influence of associated chronic metabolic disorders, this tissue changes its activity. It starts to release a lot of pro-inflammatory molecules and leads to the disturbance of the local metabolism of cardiac cells. It can initiate the processes of fibrosis, which impairs the structure of the heart and leads to disturbances in its mechanical function.

The resultant conditions may contribute to the development of at least two very widely recognized cardiac diseases in our society: atrial fibrillation and heart failure. In case of the former, tissue remodeling and fibrosis lead to electrical chaos. Conversely, in patients with heart failure (specifically its special and increasingly frequent variant with preserved ejection fraction), the heart retains the ability to pump the blood, but becomes rigid due to chronic inflammation. It is because of this increasing rigidity that the heart cannot properly relax and fill.

Ablation is not a definitive solution

Currently, percutaneous ablation constitutes the gold standard in the treatment of atrial fibrillation. It involves the electrical isolation of the pulmonary veins from the heart. We know that this area is very arrhythmogenic and it initiates abnormal impulses leading to fibrillation. Percutaneous ablation is currently the best available treatment modality for this type of arrhythmia. However, it should be remembered that the procedure serves only to maintain normal heart rhythm, and not to completely remove the primary cause underlying the disease.

Atrial fibrillation is actually the tip of the iceberg, with a number of different processes hiding under the surface of the water. Arrhythmia is seldom a purely electrical defect dependent on the aforementioned pulmonary veins. It is often a manifestation of chronic inflammation and tissue remodeling in the atria, which lose their healthy structure. In everyday practice around the world, it is observed that a fairly large proportion of patients experience the recurrence of arrhythmia despite ablation.

Our previous research showed that abnormal pathological parameters of epicardial adipose tissue may significantly worsen the results of ablation. Chronic inflammation generated by this fat contributes to progressive anatomical changes in the heart. If we do not control this local inflammation and metabolic disorders, even the best performed procedure may be insufficient to maintain a normal rhythm for many years.

The same principle applies to patients with heart failure with preserved ejection fraction, where an uncontrolled inflammatory process in the epicardial adipose tissue constantly drives rigidity, fibrosis, and myocardial remodeling. This leads to the deterioration of our physical capacity, shortness of breath and fatigability.

"Liquid biopsy" and search for a molecular trace

To combat heart failure and atrial fibrillation more effectively and better predict their recurrence, we need to gain more thorough understanding of the underlying biochemical processes. In research projects conducted at the Medical University of Warsaw, we focus on the non-invasive assessment of the pathological remodeling of the epicardial fat.

Importantly, the global scientific community has so far focused mainly on the volume of this fat, assuming that the more of it there is, the worse it is. In our research, we use computed tomography to additionally assess its "quality". It is done through the so-called attenuation, which may assess the inflammation occurring within.

Our goal is also to verify the concept of "liquid biopsy". We examine whether the pathological and pro-inflammatory activity of the epicardial adipose tissue leaves a tangible, measurable trace in the patient's blood, that could be easily detectable during a standard blood collection in the doctor's office. For that reason:

• we search for specific lipid molecules (microscopic products of abnormal cellular metabolism, e.g., ceramides) that are released into the bloodstream from the inflamed adipose tissue,
• we assess the concentrations of proteins responsible for lipid transport and the inflammatory response of the body,
• we verify the concentration of substances that may constitute an early indicator of damage or mechanical remodeling of the heart.

The future: treatment aimed at the underlying cause of the disease

In the future, the identification of circulating biomarkers will allow the identification of patients being at the highest risk of ablation failure even before entering the procedure room. As a result, we will be able to implement targeted pharmacological treatment earlier and wiser, and modify the patient's lifestyle before irreversible changes in the structure of the heart occur. This offers great hope for the future that patients may be protected from developing atrial fibrillation and, consequently, from having to undergo an invasive procedure.

The implementation of such a procedure is possible today. Although we do not yet have drugs that target the epicardial tissue specifically and exclusively, we can successfully use commonly available cardiometabolic drugs (such as flozins, incretin-based drugs or statins) in patients with obesity or diabetes. Their documented soothing and calming effect on systemic inflammation translates into a better prognosis.

Over time, medicine may advance even further, towards modern interventions targeting the epicardial adipose tissue directly and locally. It is still a matter for the future, but in cardiology it is certainly worth looking that far ahead.

The research described in this text is carried out at the Medical University of Warsaw and financed under the "Miniatura 10" grant of the National Science Centre and the Young Investigator Grants of the Medical University of Warsaw – editions 2024/2025 and 2025/2026.