Heart failure and atrial fibrillation may be more closely linked than previously thought, according to research published in Nature Cardiovascular Research on Mar. 26. The study reveals that both conditions share underlying genetic and molecular mechanisms, challenging the idea that they are distinct diseases.
This finding is significant because heart failure and atrial fibrillation are two common cardiovascular disorders that often occur together. Patients with both conditions tend to have worse outcomes, but until now, the biological connection between them was not well understood.
Ivan Moskowitz, MD, PhD, a pediatric cardiologist and pathologist at the University of Chicago Medicine, said: "This intersection between two very common, very important diseases - both of which cause a lot of morbidity and mortality and billions of dollars in annual healthcare costs - has been called an 'epidemic in cardiology,' yet our understanding has remained very limited." The new study builds on previous research by Moskowitz's team using mouse models. When researchers increased activity of a gene linked to human heart failure in mice, they unexpectedly observed symptoms consistent with atrial fibrillation instead.
The gene TBX5 emerged as central to these findings. TBX5 is responsible for regulating other genes within cells. Reduced levels of TBX5 in the atria led to changes similar to those seen in heart failure models. "That made us think that diminished TBX5 may be important in heart failure," Moskowitz said. Further analysis showed over 100 other transcription factors were altered similarly across both conditions.
Using single-cell analysis techniques, researchers identified specific cell types—cardiomyocytes and fibroblasts—involved in these disease processes within the human atrium. These results suggest multiple cell types interact during disease progression.
Moskowitz argued for a shift in perspective: "The coordinated change in transcription factors lead us to conclude that atrial fibrillation is not really a different disease than heart failure; it is just what we might call 'atrial heart failure,' a manifestation of which is atrial fibrillation." He added: "Instead of a rhythm disorder in the atria, we can understand it more like an atrial myopathy that is mimicking what's happening in ventricle cells in heart failure." This could affect how treatments are developed for these patients moving forward.
Ongoing work at UChicago Medicine aims to further analyze these pathways and explore whether restoring disrupted signaling genes can prevent arrhythmias from developing. "This intersection is a fertile ground for insight into atrial fibrillation and how it may be treated," Moskowitz said.
