Atrial fibrillation is the most common sustained cardiac arrhythmia worldwide. According to the German Heart Foundation, around 1.8 million people in Germany alone are affected. Atrial fibrillation is caused by disorganised electrical activity in the atria of the heart. As a result, the heart beats irregularly and often too quickly. Many patients suffer from palpitations, shortness of breath, reduced physical performance, or fatigue. Particularly problematic is the so-called persistent form of atrial fibrillation, in which the arrhythmia no longer terminates spontaneously. Over time, this leads to structural and functional changes in the cardiac tissue. The condition significantly increases the risk of stroke, heart failure, and premature death. To date, research and treatment have focused primarily on the left atrium and the pulmonary veins opening into it, which are regarded as major triggers of atrial fibrillation.
A research team led by Dr Niels Voigt, Professor of Molecular Pharmacology at the Institute of Pharmacology and Toxicology at the University Medical Center Göttingen (UMG), and Dr Christof Lenz, Head of the Proteomics Service Unit at the Faculty of Medicine of the Georg August University Göttingen, together with Dr Aiste Liutkute, investigated whether and to what extent the right atrium is also affected in long-standing atrial fibrillation. The study shows that the right atrium likewise undergoes profound remodelling processes and increasingly resembles the left atrium.
“Our study findings suggest that persistent atrial fibrillation should be understood as a disease affecting both atria,” says Dr Liutkute, first author of the study. “This may also explain why established therapies for long-standing atrial fibrillation are often not successful in the long term.”
The findings may also have implications for clinical treatment. Current therapeutic approaches focus predominantly on the left atrium. “Our data suggest that both atria may need to be considered more closely in future,” says Dr Lenz.
Measuring the Entire Set of Cardiac Proteins
The research team analysed tissue samples from the right and left atria of patients with persistent atrial fibrillation, which had been obtained during cardiac surgery. Samples from non-transplanted donor hearts without known cardiac arrhythmias served as the control group.
Using mass spectrometry techniques, the scientists simultaneously examined thousands of proteins in order to identify disease-related changes in cardiac tissue. Mass spectrometry is a high-resolution analytical method that enables molecules to be identified and quantified precisely according to their mass. This makes it possible to determine which proteins are present in cardiac muscle cells and how their composition changes in disease. For the study, the researchers first created a comprehensive reference library of the human cardiac proteome. The proteome refers to the complete set of proteins present in a tissue or cell. Proteins perform essential functions in the body and provide insight into which biological processes are active within cells. In addition to the proteomic analyses, the team microscopically examined scarring of the cardiac tissue, confirmed notable protein alterations using biochemical methods, and measured blood markers indicative of cardiac stress.
The right atrium is affected in a similar way to the left
The analyses showed that in persistent atrial fibrillation, the right atrium exhibits pathological changes similar to those seen in the left atrium. In both atria, the researchers identified increased tissue scarring, degradation of important cardiac muscle structures, and clear signs of cellular stress and remodelling processes. These changes impair the normal electrical conduction within the heart and may contribute to the persistence of atrial fibrillation. At the same time, many of the molecular differences that normally distinguish the right and left atria disappeared. The right atrium lost protein markers characteristic of its identity and increasingly adopted features of the left atrium, including proteins associated with altered energy metabolism and structural remodelling of cardiac muscle cells.
The study was conducted at the UMG in collaboration with international partners.
Source: Press release UMG
Original publication:
Liutkute A, Berrandou TE, Kestel S, et al. Mass spectrometric proteome profiling using a deep spectral library reveals homogenization of right and left atrial proteomes in persistent atrial fibrillation patients. Cardiovasc Res. Published online April 2, 2026. doi:10.1093/cvr/cvag076
