Atrial fibrillation is the most common cardiac arrhythmia in older people. It often occurs in patients with concomitant cardiovascular diseases that are based on the same disease mechanisms. Little is known about the actual disease processes that lead to atrial fibrillation-related complications and their interactions in those affected.
The EAST - AFNET 4 study (Early Treatment of Atrial Fibrillation for Stroke Prevention) has shown that early rhythm maintenance - with antiarrhythmic drugs or atrial fibrillation ablation - within one year of the diagnosis of atrial fibrillation achieved better results than conventional treatment in 2789 patients with early atrial fibrillation and cardiovascular risk factors over a period of five years. A series of sub-analyses of the EAST - AFNET 4 dataset verified the results for different subgroups.
This substudy investigated whether biomolecules circulating in patients' blood can be used to measure atrial fibrillation-typical disease processes and their interactions, and how they relate to stroke, heart failure, acute coronary syndrome and cardiovascular death. Paulus Kirchhof, principal investigator of EAST - AFNET 4 and author of the study, explains: "We were fortunate to be able to accurately quantify thirteen biomolecules associated with different disease processes in the EAST - AFNET 4 biomolecule study. Clustering methods, which capture interactions between biomolecules, were used to identify patients at risk of cardiovascular events based on biomolecule concentrations. In this way, four sub-phenotypes of atrial fibrillation with different biomolecule profiles and an increased risk of complications were identified. The results provide information about the factors that lead to complications in patients with atrial fibrillation."
The pre-specified analysis of the EAST - AFNET4 biomolecule study categorised 1586 patients (71 years old, 46% women) into four groups based on blood concentrations of thirteen precisely quantified biomolecules. These biomarkers may reflect ageing, cardiac fibrosis, metabolic disorders, oxidative stress, cardiac stress, endothelial dysfunction and inflammation. In each patient cluster, the incidence of cardiovascular death, stroke or hospitalisation for heart failure or acute coronary syndrome was calculated and compared between clusters over a mean period of 5.1 years. The results were independently validated in a prospective cohort of 748 patients with atrial fibrillation (BBC-AF; median follow-up 2.9 years).
The group of patients with the highest risk mainly showed cardiometabolic disorders, with increased concentrations of the biomolecules BMP10, IGFBP7, NT-proBNP, ANGPT2 and GDF15. The patients in the lowest-risk cluster had low concentrations of these biomolecules. Two medium-risk clusters were distinguished by high or low concentrations of hsCRP, IL-6 and D-dimer. People in the highest risk group were five times more likely to have cardiovascular complications than those in the lowest risk group. Early rhythm maintenance was effective in all clusters.
Prof Fabritz concludes: "The EAST - AFNET 4 biomolecule study has shown that biomolecule concentrations can be used to identify certain characteristics in patients with atrial fibrillation with high and low cardiovascular risk. The patient clusters defined on the basis of biomolecules can contribute to improving the treatment of atrial fibrillation. Our results call for further research on the effects of biomolecules on cardiovascular function. These patient clusters open up new treatment options in each group and allow research into efficacy in patients with specific risk characteristics."
The EAST - AFNET 4 biomolecule substudy was conducted on an international level in collaboration with the European research consortia CATCH ME and MAESTRIA.
Further information on the Atrial Fibrillation Network
Link to the original publication: Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk: EAST-AFNET 4 biomolecule study (Fabritz et al., 2024)
