RESUMO
BACKGROUND AND AIMS: In patients with atrial fibrillation (AF), recurrent AF and sinus rhythm during follow-up are determined by interactions between cardiovascular disease processes and rhythm-control therapy. Predictors of attaining sinus rhythm at follow-up are not well known. METHODS: To quantify the interaction between cardiovascular disease processes and rhythm outcomes, 14 biomarkers reflecting AF-related cardiovascular disease processes in 1586 patients in the EAST-AFNET 4 biomolecule study (71 years old, 46% women) were quantified at baseline. Mixed logistic regression models including clinical features were constructed for each biomarker. Biomarkers were interrogated for interaction with early rhythm control. Outcome was sinus rhythm at 12 months. Results were validated at 24 months and in external datasets. RESULTS: Higher baseline concentrations of three biomarkers were independently associated with a lower chance of sinus rhythm at 12 months: angiopoietin 2 (ANGPT2) (odds ratio [OR] 0.76 [95% confidence interval 0.65-0.89], p=0.001), bone morphogenetic protein 10 (BMP10) (OR 0.83 [0.71-0.97], p=0.017) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (OR 0.73 [0.60-0.88], p=0.001). Analysis of rhythm at 24 months confirmed the results. Early rhythm control interacted with the predictive potential of NT-proBNP (pinteraction=0.033). The predictive effect of NT-proBNP was reduced in patients randomized to early rhythm control (usual care: OR 0.64 [0.51-0.80], p<0.001; early rhythm control: OR 0.90 [0.69-1.18], p=0.453). External validation confirmed that low concentrations of ANGPT2, BMP10 and NT-proBNP predict sinus rhythm during follow-up. CONCLUSIONS: Low concentrations of ANGPT2, BMP10 and NT-proBNP identify patients with AF who are likely to attain sinus rhythm during follow-up. The predictive ability of NT-proBNP is attenuated in patients receiving rhythm control.
RESUMO
Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by cognitive, affective, and motor dysfunction. The main pathophysiological mechanisms are chronic neuroinflammation, hyper-phosphorylated tau (p-tau) accumulation and neurodegeneration. CTE is mostly caused by exposure to multiple mild traumatic brain injuries, placing people participating in, for example, high contact sports at increased risk. Currently, CTE can solely be diagnosed post mortem based on the spatial pattern of tau-accumulation. Herein, we review candidate imaging and molecular biomarkers for their sensitivity and specificity and we look whether these are sufficient for reliable ante mortem diagnosis. Of the imaging biomarkers, PET appears to have the best potential. Candidate fluid biomarkers consist of genes and proteins found in brain derived extracellular vesicles, as well as cerebrospinal fluid (CSF) p-tau levels. However, neither these biomarkers nor the imaging biomarkers have the discriminatory power to differentiate between CTE and other tauopathies, highlighting the need for further validation. Future research could incorporate machine learning methodologies to differentiate between the tau accumulation patterns detected by PET/fMRI in Alzheimer's and CTE patients. Additionally, proteomic and metabolomic profiling of CSF and plasma associated with chronic mild traumatic brain injuries could highlight potential biomarkers for identifying at risk patients.