New study explores the connection between chronic inflammation and arrhythmia development, identifying potential therapeutic targets

A recent Brazilian study published in Nature Cardiovascular Research has highlighted promising pathways for preventing and treating atrial fibrillation, a condition that significantly raises the risks of stroke and dementia. The research was led by the Federal University of Rio de Janeiro (UFRJ) in partnership with the D’Or Institute for Research and Education (IDOR).

What Is Atrial Fibrillation?

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. It disrupts the normal rhythm of the heart, causing irregular and often rapid heartbeats. This condition is associated with increased risks of stroke, dementia, and heart failure. It is also linked to other health issues like hypertension, obesity, and sleep apnea, which can exacerbate its severity.

Although AF is more prevalent among older adults—affecting roughly 10% of people over 80—its diagnosis is on the rise among younger populations, driven by lifestyle changes and chronic stress. Despite its prevalence, the underlying causes of AF are often unclear, posing challenges to effective treatment.

Addressing this complexity, the study investigated how chronic inflammation might act as a direct trigger for AF, paving the way for specific therapies and targeted medications.

Chronic Inflammation and Atrial Fibrillation

Chronic inflammation is a common denominator in many conditions associated with AF. However, the exact mechanisms linking inflammation to arrhythmia have remained elusive. According to study leader Dr. Emiliano Medei, a researcher at IDOR and UFRJ, interleukin-1 beta (IL-1β)—a molecule of the immune system involved in regulating inflammation—can directly influence the heart’s electrical activity, creating a predisposition to AF.

“The present work marks a key scientific milestone in the field of knowledge. Many review papers had already suggested that IL-1β could play a vital role in atrial fibrillation. We were able to demonstrate that this actually happens,” explains Dr. Medei.

The research team began by analyzing the immunological profiles of 92 patients, including 30 healthy controls and 62 individuals diagnosed with AF, all recruited from the D’Or São Luiz hospital network. Their findings provided a solid foundation for further exploration using animal models.

Testing Atrial Fibrillation in Mice

To delve deeper, the researchers used mice to investigate the effects of IL-1β. By administering controlled doses of IL-1β over 15 days, they simulated prolonged systemic inflammation. The mice developed cardiac alterations that made them more susceptible to AF.

Additionally, the team employed genetically modified mice lacking IL-1β receptors in macrophages—immune cells found throughout the body, including the heart. These animals did not develop AF, demonstrating that IL-1β triggers the condition by activating its receptors on macrophages.

“In addition to demonstrating that IL-1β is associated with atrial fibrillation, we were able to show through which immune system cell it acts—the macrophages. Certainly, this ‘double discovery’ will contribute to new therapeutic perspectives for this highly complex disease” Dr. Medei remarks.

IL-1β as a Target for Atrial Fibrillation Therapies

Identifying IL-1β as a trigger for AF has far-reaching implications. Clinically, it is not always possible to pinpoint the specific cause of AF in each patient. However, understanding that a single factor, such as IL-1β, plays a role across various scenarios provides a clearer therapeutic target.

The study also opens new avenues for treatment. Medications that inhibit IL-1β or caspase-1—the enzyme that activates IL-1β production—are promising candidates to prevent AF in at-risk patients, particularly those with chronic inflammatory conditions.

With an aging global population and rising prevalence of conditions associated with AF, effective prevention and treatment strategies are critical public health priorities. This study offers valuable insights into the connections between the immune system and heart function, presenting innovative opportunities to tackle AF.

Written by Maria Eduarda Ledo de Abreu.

Written by Maria Eduarda Ledo de Abreu.
Illustration: Storyset

Updated March 2025: The study was featured on the cover of the March issue of Nature Cardiovascular Research